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1.
Front Public Health ; 10: 787299, 2022.
Article in English | MEDLINE | ID: covidwho-1775992

ABSTRACT

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.


Subject(s)
Acne Vulgaris , Drug Resistance, Bacterial , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Drug Resistance, Bacterial/genetics , Humans , Macrolides/pharmacology , Macrolides/therapeutic use , Microbial Sensitivity Tests
2.
Sci Total Environ ; 832: 155090, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1773765

ABSTRACT

The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25 × and 0.5 × Minimum Inhibitory Concentration, MIC) or inhibitory (1 × and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20-167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment.


Subject(s)
COVID-19 , Disinfectants , Disinfectants/toxicity , Drug Resistance, Bacterial/genetics , Escherichia coli/genetics , Humans , Microbial Sensitivity Tests , Pandemics , Quaternary Ammonium Compounds/pharmacology
3.
PLoS One ; 17(3): e0266025, 2022.
Article in English | MEDLINE | ID: covidwho-1765540

ABSTRACT

Salmonella enterica is the most common foodborne pathogen worldwide. It causes two types of diseases, a self-limiting gastroenteritis and an invasive, more threatening, infection. Salmonella gastroenteritis is caused by several serotypes and is common worldwide. In contrast, invasive salmonellosis is rare in high-income countries (HIC) while frequent in low- and middle-income countries (LMIC), especially in sub-Saharan Africa (sSA). Invasive Nontyphoidal Salmonella (iNTS), corresponding to serotypes other than Typhi and Paratyphi, have emerged in sSA and pose a significant risk to public health. We conducted a whole-genome sequence (WGS) analysis of 72 strains of Salmonella isolated from diarrheic human patients and chicken meat sold in multipurpose markets in Dakar, Senegal. Antimicrobial susceptibility testing combined with WGS data analysis revealed frequent resistance to fluoroquinolones and the sulfamethoxazole-trimethoprim combination that are among the most used treatments for invasive Salmonella. In contrast, resistance to the historical first-line drugs chloramphenicol and ampicillin, and to cephalosporins was rare. Antimicrobial resistance (AMR) was lower in clinical isolates compared to chicken strains pointing to the concern posed by the excessive use of antimicrobials in farming. Phylogenetic analysis suggested possible transmission of the emerging multidrug resistant (MDR) Kentucky ST198 and serotype Schwarzengrund from chicken to human. These results stress the need for active surveillance of Salmonella and AMR in order to address invasive salmonellosis caused by nontyphoidal Salmonella strains and other important bacterial diseases in sSA.


Subject(s)
Gastroenteritis , Salmonella Infections , Animals , Anti-Bacterial Agents/pharmacology , Chickens , Drug Resistance, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Gastroenteritis/microbiology , Genomics , Humans , Microbial Sensitivity Tests , Phylogeny , Salmonella , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Senegal/epidemiology
4.
J Med Virol ; 94(4): 1670-1688, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718413

ABSTRACT

Bangladesh is experiencing a second wave of COVID-19 since March 2021, despite the nationwide vaccination drive with ChAdOx1 (Oxford-AstraZeneca) vaccine from early February 2021. Here, we characterized 19 nasopharyngeal swab (NPS) samples from COVID-19 suspect patients using genomic and metagenomic approaches. Screening for SARS-CoV-2 by reverse transcriptase polymerase chain reaction and metagenomic sequencing revealed 17 samples of COVID-19 positive (vaccinated = 10, nonvaccinated = 7) and 2 samples of COVID-19 negative. We did not find any significant correlation between associated factors including vaccination status, age or sex of the patients, diversity or abundance of the coinfected organisms/pathogens, and the abundance of SARS-CoV-2. Though the first wave of the pandemic was dominated by clade 20B, Beta, V2 (South African variant) dominated the second wave (January 2021 to May 2021), while the third wave (May 2021 to September 2021) was responsible for Delta variants of the epidemic in Bangladesh including both vaccinated and unvaccinated infections. Noteworthily, the receptor binding domain (RBD) region of S protein of all the isolates harbored similar substitutions including K417N, E484K, and N501Y that signify the Beta, while D614G, D215G, D80A, A67V, L18F, and A701V substitutions were commonly found in the non-RBD region of Spike proteins. ORF7b and ORF3a genes underwent a positive selection (dN/dS ratio 1.77 and 1.24, respectively), while the overall S protein of the Bangladeshi SARS-CoV-2 isolates underwent negative selection pressure (dN/dS = 0.621). Furthermore, we found different bacterial coinfections like Streptococcus agalactiae, Neisseria meningitidis, Elizabethkingia anophelis, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Pseudomonas plecoglossicida, expressing a number of antibiotic resistance genes such as tetA and tetM. Overall, this approach provides valuable insights on the SARS-CoV-2 genomes and microbiome composition from both vaccinated and nonvaccinated patients in Bangladesh.


Subject(s)
COVID-19/virology , Metagenomics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Bacterial Infections/virology , Bangladesh/epidemiology , COVID-19/epidemiology , COVID-19/microbiology , COVID-19/prevention & control , Coinfection/epidemiology , Coinfection/microbiology , Coinfection/virology , Drug Resistance, Bacterial/genetics , Female , Genome, Bacterial/genetics , Genome, Viral/genetics , Humans , Male , Microbiota/genetics , Middle Aged , Mutation , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Selection, Genetic , Vaccination , Viral Proteins/genetics , Young Adult
5.
Environ Toxicol Chem ; 41(3): 687-714, 2022 03.
Article in English | MEDLINE | ID: covidwho-1706213

ABSTRACT

River ecosystems are very important parts of the water cycle and an excellent habitat, food, and drinking water source for many organisms, including humans. Antibiotics are emerging contaminants which can enter rivers from various sources. Several antibiotics and their related antibiotic resistance genes (ARGs) have been detected in these ecosystems by various research programs and could constitute a substantial problem. The presence of antibiotics and other resistance cofactors can boost the development of ARGs in the chromosomes or mobile genetic elements of natural bacteria in rivers. The ARGs in environmental bacteria can also be transferred to clinically important pathogens. However, antibiotics and their resistance genes are both not currently monitored by national or international authorities responsible for controlling the quality of water bodies. For example, they are not included in the contaminant list in the European Water Framework Directive or in the US list of Water-Quality Benchmarks for Contaminants. Although ARGs are naturally present in the environment, very few studies have focused on non-impacted rivers to assess the background ARG levels in rivers, which could provide some useful indications for future environmental regulation and legislation. The present study reviews the antibiotics and associated ARGs most commonly measured and detected in rivers, including the primary analysis tools used for their assessment. In addition, other factors that could enhance antibiotic resistance, such as the effects of chemical mixtures, the effects of climate change, and the potential effects of the coronavirus disease 2019 pandemic, are discussed. Environ Toxicol Chem 2022;41:687-714. © 2022 SETAC.


Subject(s)
COVID-19 , Rivers , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , China , Drug Resistance, Bacterial/genetics , Ecosystem , Genes, Bacterial , Humans , Rivers/chemistry , SARS-CoV-2
6.
Int J Mol Sci ; 22(22)2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1534090

ABSTRACT

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.


Subject(s)
Antitubercular Agents/chemistry , Mycobacterium tuberculosis/drug effects , Triterpenes/chemistry , Tuberculosis/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/pharmacology , DNA-Directed RNA Polymerases/antagonists & inhibitors , DNA-Directed RNA Polymerases/genetics , Drug Design , Drug Resistance, Bacterial/genetics , Humans , Molecular Docking Simulation , Molecular Structure , Mycobacterium tuberculosis/pathogenicity , Rifampin/pharmacology , Triterpenes/pharmacology , Tuberculosis/genetics , Tuberculosis/microbiology
7.
Int J Mol Sci ; 22(22)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1534089

ABSTRACT

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Drug Resistance, Bacterial/genetics , Peptides/pharmacology , Acinetobacter Infections/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/pathogenicity , Anti-Infective Agents, Local/pharmacology , Biofilms/drug effects , Carbapenems/adverse effects , Carbapenems/pharmacology , Humans , Microbial Sensitivity Tests
8.
Microbiol Spectr ; 9(2): e0019721, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1381169

ABSTRACT

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic variants that may alter viral fitness highlights the urgency of widespread next-generation sequencing (NGS) surveillance. To profile genetic variants of the entire SARS-CoV-2 genome, we developed and clinically validated a hybridization capture SARS-CoV-2 NGS assay, integrating novel methods for panel design using double-stranded DNA (dsDNA) biotin-labeled probes, and built accompanying software. This test is the first hybrid capture-based NGS assay given Food and Drug Administration (FDA) emergency use authorization for detection of the SARS-CoV-2 virus. The positive and negative percent agreement (PPA and NPA, respectively) were defined in comparison to the results for an orthogonal real-time reverse transcription polymerase chain reaction (RT-PCR) assay (PPA and NPA, 96.7 and 100%, respectively). The limit of detection was established to be 800 copies/ml with an average fold enrichment of 46,791. Furthermore, utilizing the research-use-only analysis to profile the variants, we identified 55 novel mutations, including 11 in the functionally important spike protein. Finally, we profiled the full nasopharyngeal microbiome using metagenomics and found overrepresentation of 7 taxa and evidence of macrolide resistance in SARS-CoV-2-positive patients. This hybrid capture NGS assay, coupled with optimized software, is a powerful approach to detect and comprehensively map SARS-CoV-2 genetic variants for tracking viral evolution and guiding vaccine updates. IMPORTANCE This is the first FDA emergency-use-authorized hybridization capture-based next-generation sequencing (NGS) assay to detect the SARS-CoV-2 genome. Viral metagenomics and the novel hybrid capture NGS-based assay, along with its research-use-only analysis, can provide important genetic insights into SARS-CoV-2 and other emerging pathogens and improve surveillance and early detection, potentially preventing or mitigating new outbreaks. Better understanding of the continuously evolving SARS-CoV-2 viral genome and the impact of genetic variants may provide individual risk stratification, precision therapeutic options, improved molecular diagnostics, and population-based therapeutic solutions.


Subject(s)
Genetic Variation/genetics , Genome, Viral/genetics , Microbiota/genetics , Nasopharynx/microbiology , SARS-CoV-2/genetics , Anti-Bacterial Agents/pharmacology , COVID-19/pathology , Drug Resistance, Bacterial/genetics , High-Throughput Nucleotide Sequencing , Humans , Limit of Detection , Macrolides/pharmacology , Metagenomics/methods , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification
9.
Genome Med ; 12(1): 113, 2020 12 09.
Article in English | MEDLINE | ID: covidwho-964565

ABSTRACT

BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. METHODS: Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. RESULTS: Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). CONCLUSIONS: The combination of extensive drug resistance and virulence, partly conferred through a "mosaic" plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Iron/metabolism , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Bacterial Proteins/genetics , Biofilms/growth & development , Disease Outbreaks , Genes, Bacterial/genetics , Germany/epidemiology , Humans , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/classification , Klebsiella pneumoniae/growth & development , Phylogeny , Plasmids , Polymorphism, Single Nucleotide , Virulence/drug effects , Virulence/genetics , Virulence Factors/genetics , Whole Genome Sequencing
10.
J Infect Dev Ctries ; 15(1): 58-68, 2021 Jan 31.
Article in English | MEDLINE | ID: covidwho-1079734

ABSTRACT

INTRODUCTION: SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico. METHODOLOGY: Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done. RESULTS: Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus. CONCLUSIONS: Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients.


Subject(s)
Acinetobacter Infections/transmission , Acinetobacter baumannii/isolation & purification , COVID-19/prevention & control , Cross Infection/prevention & control , Intensive Care Units , Acinetobacter baumannii/pathogenicity , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Cross Infection/microbiology , Drug Resistance, Bacterial/genetics , Equipment and Supplies/microbiology , Genotype , Humans , Interspersed Repetitive Sequences , Mexico , Pneumonia, Ventilator-Associated/microbiology
11.
Antimicrob Resist Infect Control ; 10(1): 21, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-1054843

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is a growing global problem to which the ongoing COVID-19 pandemic may further contribute. With resources deployed away from antimicrobial stewardship, evidence of substantial pre-emptive antibiotic use in COVID-19 patients and indirectly, with deteriorating economic conditions fuelling poverty potentially impacting on levels of resistance, AMR threat remains significant. MAIN BODY: In this paper, main AMR countermeasures are revisited and priorities to tackle the issue are re-iterated. The need for collaboration is stressed, acknowledging the relationship between human health, animal health and environment ("One Health" approach). Among the stated priorities, the initiative by the European Medicines Regulatory Network to further strengthen the measures in combatting AMR is highlighted. Likewise, it is asserted that other emerging health threats require global collaboration with the One Health approach offering a valuable blueprint for action. CONCLUSION: The authors stress the importance of an integrated preparedness strategy to tackle this public health peril.


Subject(s)
Anti-Bacterial Agents/pharmacology , COVID-19/epidemiology , Drug Resistance, Bacterial/genetics , One Health/legislation & jurisprudence , Pandemics , SARS-CoV-2/pathogenicity , Animal Feed/analysis , Animal Welfare/legislation & jurisprudence , Animals , Antimicrobial Stewardship/legislation & jurisprudence , Bacteria/drug effects , Bacteria/genetics , Bacteria/pathogenicity , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Europe/epidemiology , Humans , International Cooperation , Livestock/microbiology
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