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1.
Front Public Health ; 10: 794513, 2022.
Article in English | MEDLINE | ID: covidwho-1775996

ABSTRACT

Aquatic environments, under frequent anthropogenic pressure, could serve as reservoirs that provide an ideal condition for the acquisition and dissemination of antibiotic resistance genetic determinants. We investigated the prevalence and diversity of antibiotic-resistant Escherichia coli by focusing on their genetic diversity, virulence, and resistance genes in anthropogenic-impacted Larut River. The abundance of E. coli ranged from (estimated count) Est 1 to 4.7 × 105 (colony-forming units per 100 ml) CFU 100 ml-1 to Est 1 to 4.1 × 105 CFU 100 ml-1 with phylogenetic group B1 (46.72%), and A (34.39%) being the most predominant. The prevalence of multiple antibiotic resistance phenotypes of E. coli, with the presence of tet and sul resistance genes, was higher in wastewater effluents than in the river waters. These findings suggested that E. coli could be an important carrier of the resistance genes in freshwater river environments. The phylogenetic composition of E. coli and resistance genes was associated with physicochemical properties and antibiotic residues. These findings indicated that the anthropogenic inputs exerted an effect on the E. coli phylogroup composition, diversification of multiple antibiotic resistance phenotypes, and the distribution of resistance genes in the Larut River.


Subject(s)
Drug Resistance, Bacterial , Escherichia coli , Rivers , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Escherichia coli/genetics , Malaysia , Phylogeny , Prevalence , Rivers/microbiology
2.
Sci Rep ; 12(1): 2803, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1735270

ABSTRACT

The COVID-19 pandemic has demonstrated the real need for mechanisms to control the spread of airborne respiratory pathogens. Thus, preventing the spread of disease from pathogens has come to the forefront of the public consciousness. This has brought an increasing demand for novel technologies to prioritise clean air. In this study we report on the efficacy of novel biocide treated filters and their antimicrobial activity against bacteria, fungi and viruses. The antimicrobial filters reported here are shown to kill pathogens, such as Candida albicans, Escherichia coli and MRSA in under 15 min and to destroy SARS-CoV-2 viral particles in under 30 s following contact with the filter. Through air flow rate testing, light microscopy and SEM, the filters are shown to maintain their structure and filtration function. Further to this, the filters are shown to be extremely durable and to maintain antimicrobial activity throughout the operational lifetime of the product. Lastly, the filters have been tested in field trials onboard the UK rail network, showing excellent efficacy in reducing the burden of microbial species colonising the air conditioning system.


Subject(s)
Air Filters/microbiology , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , Air Filters/virology , Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19/virology , Candida albicans/drug effects , Chlorhexidine/analogs & derivatives , Chlorhexidine/chemistry , Chlorhexidine/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , SARS-CoV-2/drug effects , Time Factors
3.
J Nanobiotechnology ; 19(1): 458, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1577211

ABSTRACT

Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date.


Subject(s)
Anti-Bacterial Agents/chemistry , Coated Materials, Biocompatible/chemistry , Diamond/chemistry , Nanostructures/chemistry , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Copper/chemistry , Copper/pharmacology , Diamond/pharmacology , Escherichia coli/drug effects , Escherichia coli/growth & development , Nanostructures/ultrastructure , Nanotechnology , Surface Properties
4.
ACS Appl Mater Interfaces ; 14(4): 4892-4898, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1633913

ABSTRACT

This paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-CoV-2 by visible light irradiation in solution or as a solid coating on paper wipes and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups gives outstanding performance in both the killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-methyl imidazolium groups enhances the light activation process for both E. coli and SARS-CoV-2 but dampens the killing of the bacteria and eliminates the inactivation of the virus in the dark. For the studies with this oligomer in solution at a concentration of 1 µg/mL and E. coli, we obtain 3 log killing of the bacteria with 10 min of irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 µg/mL, we observe 4 log inactivation (99.99%) in 5 min of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated paper wipes and glass fiber filter supports. The SARS-CoV-2 is also inactivated by oligomer-coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/therapy , SARS-CoV-2/radiation effects , COVID-19/genetics , COVID-19/virology , Cations/pharmacology , Escherichia coli/drug effects , Escherichia coli/radiation effects , Humans , Light , Phototherapy , SARS-CoV-2/pathogenicity , Ultraviolet Rays , Virus Inactivation/drug effects , Virus Inactivation/radiation effects
5.
Microbiol Spectr ; 10(1): e0052221, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1622001

ABSTRACT

Heme-containing peroxidases are widely distributed in the animal and plant kingdoms and play an important role in host defense by generating potent oxidants. Myeloperoxidase (MPO), the prototype of heme-containing peroxidases, exists in neutrophils and monocytes. MPO has a broad spectrum of microbial killing. The difficulty of producing MPO at a large scale hinders its study and utilization. This study aimed to overexpress recombinant human MPO and characterize its microbicidal activities in vitro and in vivo. A human HEK293 cell line stably expressing recombinant MPO (rMPO) was established as a component of this study. rMPO was overexpressed and purified for studies on its biochemical and enzymatic properties, as well as its microbicidal activities. In this study, rMPO was secreted into culture medium as a monomer. rMPO revealed enzymatic activity similar to that of native MPO. rMPO, like native MPO, was capable of killing a broad spectrum of microorganisms, including Gram-negative and -positive bacteria and fungi, at low nM levels. Interestingly, rMPO could kill antibiotic-resistant bacteria, making it very useful for treatment of nosocomial infections and mixed infections. The administration of rMPO significantly reduced the morbidity and mortality of murine lung infections induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. In animal safety tests, the administration of 100 nM rMPO via tail vein did not result in any sign of toxic effects. Taken together, the data suggest that rMPO purified from a stably expressing human cell line is a new class of antimicrobial agents with the ability to kill a broad spectrum of pathogens, including bacteria and fungi with or without drug resistance. IMPORTANCE Over the past 2 decades, more than 20 new infectious diseases have emerged. Unfortunately, novel antimicrobial therapeutics are discovered at much lower rates. Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness, greater risk of death, and high health care costs. Currently, this is best seen with the lack of a cure for coronavirus disease 2019 (COVID-19). To combat such untreatable microorganisms, there is an urgent need to discover new classes of antimicrobial agents. Myeloperoxidase (MPO) plays an important role in host defense. The difficulty of producing MPO on a large scale hinders its study and utilization. We have produced recombinant MPO at a large scale and have characterized its antimicrobial activities. Most importantly, recombinant MPO significantly reduced the morbidity and mortality of murine pneumonia induced by Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Our data suggest that recombinant MPO from human cells is a new class of antimicrobials with a broad spectrum of activity.


Subject(s)
Anti-Infective Agents/pharmacology , Peroxidase/pharmacology , Acute Disease , Animals , Anti-Infective Agents/classification , Anti-Infective Agents/therapeutic use , Anti-Infective Agents/toxicity , Candida albicans/drug effects , Drug Resistance, Bacterial , Escherichia coli/drug effects , Female , HEK293 Cells , Humans , Hydrogen Peroxide/toxicity , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Mice, Inbred C57BL , Peroxidase/genetics , Peroxidase/therapeutic use , Peroxidase/toxicity , Pneumonia, Bacterial/drug therapy , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Recombinant Proteins/toxicity , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects
6.
ACS Appl Mater Interfaces ; 14(1): 49-56, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1608662

ABSTRACT

The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents. This coating minimally impacts the mechanical properties of the fabric while also imparting hydrophobicity. Passive inactivation of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) is achieved with >98% inactivation after 24 h, with a 23× and 3× inactivation rate increase against E. coli and MRSA, respectively, when green light is used to generate ROS. Up to 90% decrease in the infectivity of SARS-CoV-2 after 2 h of irradiated incubation with the material is demonstrated. These results show that modifying textiles with dual-functional polymers results in robust and highly antimicrobial materials that are expected to find widespread use in combating the spread of deadly pathogens.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Coated Materials, Biocompatible/chemistry , Polymers/chemistry , SARS-CoV-2/drug effects , Textiles/analysis , Anti-Infective Agents/chemistry , COVID-19/prevention & control , COVID-19/virology , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Textiles/toxicity , Ultraviolet Rays
7.
Microbiol Spectr ; 9(3): e0028321, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1501550

ABSTRACT

The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant Enterobacteriaceae (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. IMPORTANCE AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.


Subject(s)
Bacteria/classification , Communicable Diseases/epidemiology , Communicable Diseases/microbiology , Drug Resistance, Bacterial , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , COVID-19/epidemiology , Child , China/epidemiology , Drug Resistance, Bacterial/drug effects , Escherichia coli/drug effects , Humans , Klebsiella pneumoniae/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Moraxella catarrhalis , Pseudomonas aeruginosa/drug effects , SARS-CoV-2 , Staphylococcus aureus/drug effects , Staphylococcus epidermidis , Streptococcus pneumoniae , Streptococcus pyogenes
8.
J Am Chem Soc ; 143(43): 17891-17909, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1483091

ABSTRACT

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.


Subject(s)
Anti-Infective Agents/chemistry , Drug Design , Phototherapy/methods , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Bacteria/drug effects , Biofilms/drug effects , Biofilms/radiation effects , Coloring Agents/chemistry , Coloring Agents/pharmacology , Equipment and Supplies/microbiology , Equipment and Supplies/virology , Escherichia coli/drug effects , Escherichia coli/physiology , Eye Diseases/drug therapy , Eye Diseases/pathology , Fungi/drug effects , Graphite/chemistry , Light , Nanoparticles/chemistry , Nanoparticles/toxicity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Quantum Theory , Reactive Oxygen Species/metabolism , Viruses/drug effects
9.
Molecules ; 26(19)2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1463769

ABSTRACT

Pristine high-density bulk disks of MgB2 with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB2 powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Boron Compounds/pharmacology , Fungi/drug effects , Magnesium Compounds/pharmacology , Candida parapsilosis/drug effects , Enterococcus faecalis/drug effects , Enterococcus faecium/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Polyesters/pharmacology , Printing, Three-Dimensional , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
10.
Molecules ; 26(19)2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1463764

ABSTRACT

Due to their large possibility of the structure modification, alkylammonium gemini surfactants are a rapidly growing class of compounds. They exhibit significant surface, aggregation and antimicrobial properties. Due to the fact that, in order to achieve the desired utility effect, the minimal concentration of compounds are used, they are in line with the principle of greenolution (green evolution) in chemistry. In this study, we present innovative synthesis of the homologous series of gemini surfactants modified at the spacer by the ether group, i.e., 3-oxa-1,5-pentane-bis(N-alkyl-N,N-dimethylammonium bromides). The critical micelle concentrations were determined. The minimal inhibitory concentrations of the synthesized compounds were determined against bacteria Escherichia coli ATCC 10536 and Staphylococcus aureus ATCC 6538; yeast Candida albicans ATCC 10231; and molds Aspergillus niger ATCC 16401 and Penicillium chrysogenum ATCC 60739. We also investigated the relationship between antimicrobial activity and alkyl chain length or the nature of the spacer. The obtained results indicate that the synthesized compounds are effective microbicides with a broad spectrum of biocidal activity.


Subject(s)
Anti-Infective Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Anti-Infective Agents/chemistry , Aspergillus niger/drug effects , Candida albicans/drug effects , Escherichia coli/drug effects , Green Chemistry Technology , Micelles , Microbial Sensitivity Tests , Molecular Structure , Penicillium chrysogenum/drug effects , Quaternary Ammonium Compounds/chemistry , Staphylococcus aureus/drug effects , Surface-Active Agents/chemistry
11.
J Am Chem Soc ; 143(40): 16777-16785, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1442692

ABSTRACT

The most recent global health crisis caused by the SARS-CoV-2 outbreak and the alarming use of chemical warfare agents highlight the necessity to produce efficient protective clothing and masks against biohazard and chemical threats. However, the development of a multifunctional protective textile is still behind to supply adequate protection for the public. To tackle this challenge, we designed multifunctional and regenerable N-chlorine based biocidal and detoxifying textiles using a robust zirconium metal-organic framework (MOF), UiO-66-NH2, as a chlorine carrier which can be easily coated on textile fibers. A chlorine bleaching converted the amine groups located on the MOF linker to active N-chlorine structures. The fibrous composite exhibited rapid biocidal activity against both Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) with up to a 7 log reduction within 5 min for each strain as well as a 5 log reduction of SARS-CoV-2 within 15 min. Moreover, the active chlorine loaded MOF/fiber composite selectively and rapidly degraded sulfur mustard and its chemical simulant 2-chloroethyl ethyl sulfide (CEES) with half-lives less than 3 minutes. The versatile MOF-based fibrous composite designed here has the potential to serve as protective cloth against both biological and chemical threats.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Chemical Warfare Agents/chemistry , Chlorine/pharmacology , Metal-Organic Frameworks/pharmacology , Protective Clothing , Animals , Anti-Bacterial Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Cell Line , Chlorine/chemistry , Escherichia coli/drug effects , Halogenation , Humans , Metal-Organic Frameworks/chemical synthesis , Microbial Sensitivity Tests , Mustard Gas/analogs & derivatives , Mustard Gas/chemistry , Oxidation-Reduction , SARS-CoV-2/drug effects , Staphylococcus aureus/drug effects , Textiles , Zirconium/chemistry
12.
J Infect ; 83(6): 664-670, 2021 12.
Article in English | MEDLINE | ID: covidwho-1440201

ABSTRACT

OBJECTIVES: We investigated the impact of the COVID-19 and national pandemic response on the epidemiology of Extended Spectrum Beta-Lactamase producing E. coli (ESBL-E.coli) in France. METHODS: Individual microbiology records from clinical laboratories were analyzed between 1 January 2019 to 31 December 2020. The ESBL-E.coli rates from clinical samples of patients in primary care and nursing home residents were compared before and after the general lockdown in March 2020, according to demographic and geographical characteristics. Interrupted time series analyses were performed to detect measurable changes in the trend of ESBL-E.coli rates. RESULTS: Records covering 793,954 E. coli isolates from 1022 clinical laboratories were analyzed. In primary care, 3.1% of E. coli isolates from clinical samples were producing ESBL before March 2020 and 2.9% since May 2020 (p < 0.001). The proportion of ESBL-E.coli decreased significantly among urine cultures, females, age categories 5-19, 40-64, > 65 year-old, and in the North, West, East and South-East regions. In nursing home, the ESBL-E.coli rate was 9.3% (monthly rate min-max: 6.5-10.5%) before March 2020 and 8.3% (7.2-9.1%) since May 2020 (p < 0.001). The reduction rate accelerated from -0.04%/month to -0.22%/month from May 2020 (p < 0.001). CONCLUSION: Investigation of factors that led to the decreased proportion of ESBL-E.coli during the COVID-19 pandemic is urgently needed.


Subject(s)
COVID-19 , Escherichia coli Infections , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Communicable Disease Control , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Male , Microbial Sensitivity Tests , Middle Aged , Pandemics , Retrospective Studies , Young Adult , beta-Lactamases
13.
Biochem Biophys Res Commun ; 575: 36-41, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1370449

ABSTRACT

Air spaces and material surfaces in a pathogen-contaminated environment can often be a source of infection to humans, and disinfection has become a common intervention focused on reducing the contamination levels. In this study, we examined the efficacy of SAIW, a unique electrolyzed water with chlorine-free, high pH, high concentration of dissolved hydrogen, and low oxygen reduction potential, for the inactivation of several viruses and bacteria. Infectivity assays revealed that initial viral titers of enveloped and non-enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, herpes simplex virus type 1, human coronavirus, feline calicivirus, and canine parvovirus, were reduced by 2.9- to 5.5-log10 within 30 s of SAIW exposure. Similarly, the culturability of three Gram-negative bacteria (Escherichia coli, Salmonella, and Legionella) dropped down by 1.9- to 4.9-log10 within 30 s of SAIW treatment. Mechanistically, treatment with SAIW was found to significantly decrease the binding and subsequent entry efficiencies of SARS-CoV-2 on Vero cells. Finally, we showed that this chlorine-free electrolytic ion water had no acute inhalation toxicity in mice, demonstrating that SAIW holds promise for a safer antiviral and antibacterial disinfectant.


Subject(s)
Anti-Infective Agents/pharmacology , Disinfectants/pharmacology , Disinfection/methods , SARS-CoV-2/drug effects , Virus Inactivation/drug effects , Water/pharmacology , Animals , Calicivirus, Feline/drug effects , Calicivirus, Feline/growth & development , Chlorocebus aethiops , Colony Count, Microbial , Electrolysis , Escherichia coli/drug effects , Escherichia coli/growth & development , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/growth & development , Humans , Hydrogen-Ion Concentration , Influenza A virus/drug effects , Influenza A virus/growth & development , Legionella/drug effects , Legionella/growth & development , Mice , Parvovirus, Canine/drug effects , Parvovirus, Canine/growth & development , SARS-CoV-2/growth & development , Salmonella/drug effects , Salmonella/growth & development , Skin/drug effects , Vero Cells , Viral Load
14.
Diagn Microbiol Infect Dis ; 100(4): 115399, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1315428

ABSTRACT

Between November 2018 and October 2019, carbapenem-resistant Enterobacterales carrying New Delhi Metallo-ß-lactamase (NDM) caused one of the largest and persistent outbreaks occurred in Italy and intensified surveillance measures have been taken in all Italian hospitals. In this study we analyzed NDM-5- producing Escherichia coli identified in 2 hospitals of the Lazio region in Italy. Epidemiological and microbiological data demonstrated that in 2018-2019 the NDM-5-producing high-risk E. coli ST167 clone circulated in patients from both hospitals. In 2019, another NDM-5-producing E. coli clone, identified by MLST as ST617 was introduced in one of the 2 hospitals and caused an outbreak. This study describes an application of genomics as a useful method to discern endemic and outbreak clones when applied to strains of the same species (E. coli) with the same resistance determinant (NDM-5) and the relevance of screening patients admitted in critical units for carbapenemase producers to prevent outbreaks.


Subject(s)
Escherichia coli Infections/epidemiology , Escherichia coli/genetics , beta-Lactamases/genetics , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , DNA, Bacterial/genetics , Disease Outbreaks/prevention & control , Disease Outbreaks/statistics & numerical data , Drug Resistance, Multiple, Bacterial , Escherichia coli/drug effects , Escherichia coli/enzymology , Female , Genome, Bacterial , Hospitals/statistics & numerical data , Humans , Italy/epidemiology , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Whole Genome Sequencing , beta-Lactamases/biosynthesis
15.
BMC Pulm Med ; 20(1): 233, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-1257932

ABSTRACT

BACKGROUND: Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated. METHODS: A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI. RESULTS: Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013-2015 were 15,549 and 1671, while those in 2016-2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016-2018). CONCLUSIONS: Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.


Subject(s)
Bacterial Infections/microbiology , Bronchoalveolar Lavage Fluid/microbiology , Microbial Sensitivity Tests , Respiratory System/microbiology , Sputum/microbiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , China/epidemiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Hospitals, Teaching , Humans , Male , Retrospective Studies , Staphylococcus aureus/isolation & purification
16.
ACS Appl Mater Interfaces ; 13(11): 12912-12927, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1185365

ABSTRACT

The current pandemic caused by SARS-CoV-2 has seen a widespread use of personal protective equipment, especially face masks. This has created the need to develop better and reusable protective masks with built-in antimicrobial, self-cleaning, and aerosol filtration properties to prevent the transmission of air-borne pathogens such as the coronaviruses. Herein, molybdenum disulfide (MoS2) nanosheets are used to prepare modified polycotton fabrics having excellent antibacterial activity and photothermal properties. Upon sunlight irradiation, the nanosheet-modified fabrics rapidly increased the surface temperature to ∼77 °C, making them ideal for sunlight-mediated self-disinfection. Complete self-disinfection of the nanosheet-modified fabric was achieved within 3 min of irradiation, making the fabrics favorably reusable upon self-disinfection. The nanosheet-modified fabrics maintained the antibacterial efficiency even after 60 washing cycles. Furthermore, the particle filtration efficiency of three-layered surgical masks was found to be significantly improved through incorporation of the MoS2-modified fabric as an additional layer of protective clothing, without compromising the breathability of the masks. The repurposed surgical masks could filter out around 97% of 200 nm particles and 96% of 100 nm particles, thus making them potentially useful for preventing the spread of coronaviruses (120 nm) by trapping them along with antibacterial protection against other airborne pathogens.


Subject(s)
Anti-Infective Agents/chemistry , Disulfides/chemistry , Molybdenum/chemistry , Nanostructures/chemistry , Personal Protective Equipment , Recycling , Anti-Infective Agents/pharmacology , COVID-19/prevention & control , COVID-19/virology , Escherichia coli/drug effects , Escherichia coli/metabolism , Glutathione/chemistry , Humans , Nanostructures/toxicity , Oxidation-Reduction , Particle Size , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism , Sunlight , Temperature
17.
Bioorg Med Chem Lett ; 36: 127808, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1034180

ABSTRACT

Commercial disinfectants are routinely used to decontaminate surfaces where microbes are expected and unwelcome. Several disinfectants contain quaternary ammonium salts, or "quats", all being derived from ammonium. Quaternary alkyl dimethyl benzyl ammonium chloride or bromide disinfectants are widely available. These compounds are effective in reducing or eliminating bacteria on contaminated nonporous surfaces. A unique benzyl derived boronium salt with strong detergent action has been developed. It demonstrated 4-8X greater antibacterial activity against 3 different bacteria when compared to an equal concentration of a commercial quant disinfectant solution containing alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl ethylbenzyl ammonium chloride. Antibacterial effectiveness of each agent was determined by the minimum inhibitory concentration (MIC) method.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bromides/pharmacology , Disinfectants/pharmacology , Quaternary Ammonium Compounds/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Bromides/chemical synthesis , Bromides/chemistry , Disinfectants/chemical synthesis , Disinfectants/chemistry , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Pseudomonas aeruginosa/drug effects , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Staphylococcus aureus/drug effects , Structure-Activity Relationship
18.
Biomolecules ; 11(3)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1146390

ABSTRACT

Antimicrobial resistance is an increasing issue in healthcare as the overuse of antibacterial agents rises during the COVID-19 pandemic. The need for new antibiotics is high, while the arsenal of available agents is decreasing, especially for the treatment of infections by Gram-negative bacteria like Escherichia coli. Antimicrobial peptides (AMPs) are offering a promising route for novel antibiotic development and deep learning techniques can be utilised for successful AMP design. In this study, a long short-term memory (LSTM) generative model and a bidirectional LSTM classification model were constructed to design short novel AMP sequences with potential antibacterial activity against E. coli. Two versions of the generative model and six versions of the classification model were trained and optimised using Bayesian hyperparameter optimisation. These models were used to generate sets of short novel sequences that were classified as antimicrobial or non-antimicrobial. The validation accuracies of the classification models were 81.6-88.9% and the novel AMPs were classified as antimicrobial with accuracies of 70.6-91.7%. Predicted three-dimensional conformations of selected short AMPs exhibited the alpha-helical structure with amphipathic surfaces. This demonstrates that LSTMs are effective tools for generating novel AMPs against targeted bacteria and could be utilised in the search for new antibiotics leads.


Subject(s)
Deep Learning , Escherichia coli/drug effects , Pore Forming Cytotoxic Proteins/chemistry , Amino Acid Sequence , Area Under Curve , Bayes Theorem , Machine Learning , Molecular Conformation , Pore Forming Cytotoxic Proteins/pharmacology , Protein Conformation, alpha-Helical , ROC Curve
19.
Assay Drug Dev Technol ; 19(3): 156-175, 2021 04.
Article in English | MEDLINE | ID: covidwho-1137927

ABSTRACT

Corona virus disease-2019 (COVID-19) emerged in Wuhan, China in December 2019 and was declared as a pandemic by the World Health Organization in March 2020. Although there is no complete treatment protocol for COVID-19, studies on this topic are ongoing, and it is known that broad-spectrum antibiotics such as cephalosporins are used for coinfections and symptoms in COVID-19 patients. Studies have shown that Staphylococcus aureus and Escherichia coli bacteria can cause symptoms such as diarrhea and coinfections accompanying COVID-19. Therefore, in this study, colon-targeted cefaclor monohydrate (CEF)-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit S100 nanoparticles (NPs) were prepared using a nanoprecipitation technique. The particle sizes of the CEF-loaded NPs were between 171.4 and 198.8 nm. The encapsulation efficiency was in the range of 58.4%-81.2%. With dissolution studies, it has been concluded that formulations prepared with Eudragit S100 (E-coded) and Eudragit S100+PLGA (EP-coded) are pH-sensitive formulations and they are targetable to the colon, whereas the formulation prepared only with PLGA (P-coded) can release a higher CEF rate in the colon owing to the slow release properties of PLGA. The release kinetics were fitted to the Korsmeyer-Peppas and Weibull models. The antibacterial activity of E-, EP-, and P-coded formulations was 16-fold, 16-fold, and 2-fold higher than CEF, respectively, for S. aureus and E. coli according to the microdilution results. As a result of the time killing experiment, all formulations prepared were found to be more effective than the antibiotic itself for long periods. Consequently, all formulations prepared in this study hope to guide researchers/clinicians in treating both gram-positive and gram-negative bacteria-induced infections, as well as COVID-19 associated coinfections and symptoms.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , COVID-19/complications , Cefaclor/administration & dosage , Cefaclor/therapeutic use , Intestinal Diseases/complications , Intestinal Diseases/drug therapy , Anti-Bacterial Agents/pharmacology , Cefaclor/pharmacology , Coinfection , Drug Compounding , Escherichia coli/drug effects , Excipients , Kinetics , Microbial Sensitivity Tests , Nanoparticles , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Polymethacrylic Acids , Staphylococcus aureus/drug effects
20.
ACS Appl Mater Interfaces ; 13(11): 12912-12927, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1132024

ABSTRACT

The current pandemic caused by SARS-CoV-2 has seen a widespread use of personal protective equipment, especially face masks. This has created the need to develop better and reusable protective masks with built-in antimicrobial, self-cleaning, and aerosol filtration properties to prevent the transmission of air-borne pathogens such as the coronaviruses. Herein, molybdenum disulfide (MoS2) nanosheets are used to prepare modified polycotton fabrics having excellent antibacterial activity and photothermal properties. Upon sunlight irradiation, the nanosheet-modified fabrics rapidly increased the surface temperature to ∼77 °C, making them ideal for sunlight-mediated self-disinfection. Complete self-disinfection of the nanosheet-modified fabric was achieved within 3 min of irradiation, making the fabrics favorably reusable upon self-disinfection. The nanosheet-modified fabrics maintained the antibacterial efficiency even after 60 washing cycles. Furthermore, the particle filtration efficiency of three-layered surgical masks was found to be significantly improved through incorporation of the MoS2-modified fabric as an additional layer of protective clothing, without compromising the breathability of the masks. The repurposed surgical masks could filter out around 97% of 200 nm particles and 96% of 100 nm particles, thus making them potentially useful for preventing the spread of coronaviruses (120 nm) by trapping them along with antibacterial protection against other airborne pathogens.


Subject(s)
Anti-Infective Agents/chemistry , Disulfides/chemistry , Molybdenum/chemistry , Nanostructures/chemistry , Personal Protective Equipment , Recycling , Anti-Infective Agents/pharmacology , COVID-19/prevention & control , COVID-19/virology , Escherichia coli/drug effects , Escherichia coli/metabolism , Glutathione/chemistry , Humans , Nanostructures/toxicity , Oxidation-Reduction , Particle Size , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism , Sunlight , Temperature
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