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1.
mBio ; 13(3): e0031122, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1807324

ABSTRACT

Population genomic analysis is a powerful tool to understand the evolutionary history of pathogens and the factors contributing to the success or failure of lineages. These studies have significant implications for human health, as evident from our ongoing tracking of SARS-CoV-2. In their article, Gill et al. (J. L. Gill, J. Hedge, D. J. Wilson, and R. C. MacLean, mBio 12:e02168-21, 2021, https://doi.org/10.1128/mBio.02168-21) demonstrate the utility of pathogen genomic data by comprehensively elucidating the origin of methicillin-resistant Staphylococcus aureus ST239. To accomplish this, they leveraged newly developed tools for querying large genomic data sets. Overall, these analyses rely on the availability of representative genomic data along with their associated metadata-information about where and when samples were collected, clinical and epidemiological characteristics, and phenotypic properties. However, in many instances, these data are missing. Here, I borrow the term "meaningful use" from the Health IT field to describe the need to maximize the utility of genomic data and make suggestions for how to address the current limitations.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Biological Evolution , Genomics , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , SARS-CoV-2/genetics , Staphylococcal Infections/epidemiology
2.
ACS Chem Biol ; 17(5): 1239-1248, 2022 05 20.
Article in English | MEDLINE | ID: covidwho-1805550

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic-resistant bacterial infections acquired during hospital stays have increased. Antibiotic adjuvants are a key strategy to combat these bacteria. We have evaluated several small molecule antibiotic adjuvants that have strong potentiation with ß-lactam antibiotics and are likely inhibiting a master regulatory kinase, Stk1. Here, we investigated how the lead adjuvant (compound 8) exerts its effects in a more comprehensive manner. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with oxacillin and the adjuvant. Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up- and downregulated, respectively, in response to cotreatment. Gene ontology categories and biochemical pathways that were significantly enriched with downregulated genes involved carbohydrate utilization, such as the citrate cycle and the phosphotransferase system. One of the most populated pathways was S. aureus infection. Results from an interaction network constructed with affected gene products supported the hypothesis that Stk1 is a target of compound 8. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect due to Stk1 inhibition. These results point to this antibiotic adjuvant having potential broad therapeutic use in combatting MRSA.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Carbazoles/pharmacology , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Pandemics , Staphylococcus aureus , Transcriptome
3.
Molecules ; 27(7)2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1785835

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and responsible for causing life-threatening infections. The emergence of hypervirulent and multidrug-resistant (MDR) S. aureus strains led to challenging issues in antibiotic therapy. Consequently, the morbidity and mortality rates caused by S. aureus infections have a substantial impact on health concerns. The current worldwide prevalence of MRSA infections highlights the need for long-lasting preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine candidates and drug target proteins against the 16 strains of MRSA using reverse vaccinology and subtractive genomics approaches. Using the reverse vaccinology approach, 4 putative antigenic proteins were identified; among these, PrsA and EssA proteins were found to be more promising vaccine candidates. We applied a molecular docking approach of selected 8 drug target proteins with the drug-like molecules, revealing that the ZINC4235426 as potential drug molecule with favorable interactions with the target active site residues of 5 drug target proteins viz., biotin protein ligase, HPr kinase/phosphorylase, thymidylate kinase, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase, and pantothenate synthetase. Thus, the identified proteins can be used for further rational drug or vaccine design to identify novel therapeutic agents for the treatment of multidrug-resistant staphylococcal infection.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Vaccines , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Genomics , Humans , Ligases , Methicillin-Resistant Staphylococcus aureus/genetics , Molecular Docking Simulation , Staphylococcal Infections/prevention & control , Staphylococcus aureus , Vaccinology
4.
Front Cell Infect Microbiol ; 12: 806077, 2022.
Article in English | MEDLINE | ID: covidwho-1775644

ABSTRACT

Background: Mobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using a combination of phenotypic and molecular methods. Methods: This point prevalence survey was carried out at the Emergency unit of a tertiary care facility. The emergency unit has two zones, a general zone for non-COVID-19 patients and a dedicated COVID-19 zone for confirmed or suspected COVID-19 patients. Swabs were obtained from the mobile phones of HCWs in both zones for bacterial culture and shotgun metagenomic analysis. Metagenomic sequencing of pooled environmental swabs was conducted. RT-PCR for SARS-CoV-2 detection was carried out. Results: Bacteria contamination on culture was detected from 33 (94.2%) mobile phones with a preponderance of Staphylococcus epidermidis (n/N = 18/35), Staphylococcus hominis (n/N = 13/35), and Staphylococcus haemolyticus (n/N = 7/35). Two methicillin-sensitive and three methicillin-resistant Staphylococcus aureus, and one pan-drug-resistant carbapenemase producer Acinetobacter baumannii were detected. Shotgun metagenomic analysis showed high signature of Pseudomonas aeruginosa in mobile phone and environmental samples with preponderance of P. aeruginosa bacteriophages. Malassezia and Aspergillus spp. were the predominant fungi detected. Fourteen mobile phones and one environmental sample harbored protists. P. aeruginosa antimicrobial resistance genes mostly encoding for efflux pump systems were detected. The P. aeruginosa virulent factor genes detected were related to motility, adherence, aggregation, and biofilms. One mobile phone from the COVID-19 zone (n/N = 1/5; 20%) had positive SARS-CoV-2 detection while all other phone and environmental samples were negative. Conclusion: The findings demonstrate that mobile phones of HCWs are fomites for potentially pathogenic and highly drug-resistant microbes. The presence of these microbes on the mobile phones and hospital environmental surfaces is a concern as it poses a risk of pathogen transfer to patients and dissemination into the community.


Subject(s)
COVID-19 , Cell Phone , Methicillin-Resistant Staphylococcus aureus , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics
5.
J Hosp Infect ; 123: 52-60, 2022 May.
Article in English | MEDLINE | ID: covidwho-1757533

ABSTRACT

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs). AIM: To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs. METHODS: Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong. FINDINGS: During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital. CONCLUSION: MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Aged , COVID-19/epidemiology , Carrier State/epidemiology , Humans , Methicillin , Methicillin-Resistant Staphylococcus aureus/genetics , Pandemics , Staphylococcal Infections/epidemiology
6.
Pediatr Infect Dis J ; 41(4): e142-e145, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1752202

ABSTRACT

We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bacteremia in Danish children between 2016 and 2021. We found 2 fatal cases with preceding viral prodrome due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the usual benign course of SARS-CoV-2 infection in children, awareness of possible superinfection with PVL-SA in a child with rapid deterioration is crucial to ensure adequate treatment, including antimicrobial drugs with antitoxin effect.


Subject(s)
Bacteremia , Bacterial Toxins/biosynthesis , COVID-19/complications , Exotoxins/biosynthesis , Leukocidins/biosynthesis , SARS-CoV-2 , Staphylococcal Infections/etiology , Staphylococcal Infections/mortality , Staphylococcus aureus/genetics , Adolescent , COVID-19/virology , Child , Child, Preschool , Coinfection , Comorbidity , Denmark/epidemiology , Female , Humans , Infant , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Public Health Surveillance , Severity of Illness Index , Staphylococcal Infections/diagnosis , Staphylococcal Infections/therapy , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism
8.
PLoS One ; 15(8): e0237127, 2020.
Article in English | MEDLINE | ID: covidwho-695633

ABSTRACT

BACKGROUND: The global pandemic of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV2) has resulted in unprecedented challenges for healthcare systems. One barrier to widespread testing has been a paucity of traditional respiratory viral swab collection kits relative to the demand. Whether other sample collection kits, such as widely available MRSA nasal swabs can be used to detect SARS-CoV-2 is unknown. METHODS: We compared simultaneous nasal MRSA swabs (COPAN ESwabs ® 480C flocked nasal swab in 1mL of liquid Amies medium) and virals wabs (BD H192(07) flexible mini-tip flocked nasopharyngeal swabs in 3mL Universal Transport Medium) for SARS-CoV-2 PCR testing using Simplexa COVID-19 Direct assay on patients over a 4-day period. When the results were discordant, the viral swab sample was run again on the Cepheid Xpert Xpress ® SARS-CoV-2 assay. RESULTS: Of the 81 included samples, there were 19 positives and 62 negatives in viral media and 18 positives and 63 negative in the MRSA swabs. Amongst all included samples, there was concordance between the COPAN ESwabs ® 480C and the viral swabs in 78 (96.3%). CONCLUSION: We found a high rate of concordance in test results between COPAN ESwabs ® 480C in Amies solution and BD H192(07) nasopharyngeal swabs in in 3 mL of Universal Viral Transport medium viral media. Clinicians and laboratories should feel better informed and assured using COPAN ESwabs ® 480C to help in the diagnosis of COVID-19.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Methicillin-Resistant Staphylococcus aureus/genetics , Pneumonia, Viral/diagnosis , Specimen Handling/methods , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Humans , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Nasopharynx/microbiology , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology , RNA Stability , RNA, Bacterial/analysis , RNA, Bacterial/metabolism , RNA, Viral/analysis , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2
9.
APMIS ; 128(6): 451-462, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-155071

ABSTRACT

Bacteria and viruses were analysed in the upper respiratory tract of symptomatic pig farmers and their domestic pigs. Eighty six human nasal and 495 (50 pools) porcine snout swabs were collected in Schleswig-Holstein, Germany. Staphylococcus (S.) aureus (62.8%, 54/86), human rhino- and coronaviruses (HRV, 29.1%, 25/86; HCoV, 16.3%, 14/86) were frequently detected in humans, while Haemophilus parasuis (90.0%, 45/50), Mycoplasma hyorhinis (78.6%, 11/14), Enterovirus G (EV-G, 56.0%, 28/50) and S. aureus (36.0%, 18/50), respectively, were highly prevalent in pigs. The detection of S. aureus in human follow-up samples indicates a carrier status. The methicillin-resistant phenotype (MRSA) was identified in 33.3% (18/54) of nasal swabs and in one of 18 (5.6%) pooled snout swabs that were tested positive for S. aureus. Strains were indicative of the livestock-associated clonal complex CC398, with t011 being the most common staphylococcal protein A type. Enterobacterales and non-fermenters were frequently isolated from swabs. Their detection in follow-up samples suggests a carrier status. All were classified as being non-multiresistant. There was no example for cross-species transmission of viruses. In contrast, transmission of S. aureus through occupational contact to pigs seems possible. The study contributes to the 'One Health' approach.


Subject(s)
Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Staphylococcal Infections/veterinary , Sus scrofa/microbiology , Sus scrofa/virology , Swine Diseases/epidemiology , Animals , Carrier State , Humans , Livestock , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Nasal Mucosa/microbiology , Nasal Mucosa/virology , Occupational Diseases/microbiology , Prevalence , Respiratory Tract Infections/epidemiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/transmission , Swine , Swine Diseases/microbiology , Swine Diseases/transmission , Swine Diseases/virology , Virus Diseases/epidemiology , Virus Diseases/transmission , Virus Diseases/veterinary
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