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ST7 Becomes One of the Most Common Staphylococcus aureus Clones After the COVID-19 Epidemic in the City of Wuhan, China

Authors Gu J , Shen S, Xiong M, Zhao J, Tian H , Xiao X, Li Y

Received 11 December 2022

Accepted for publication 2 February 2023

Published 13 February 2023 Volume 2023:16 Pages 843—852

DOI https://doi.org/10.2147/IDR.S401069

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony



Jihong Gu,1,* Shucheng Shen,1,* Mengyuan Xiong,1,2 Jin Zhao,1,2 Hongpan Tian,1 Xiao Xiao,1,3 Yirong Li1– 3

1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Wuhan Research Center for Infectious Diseases and Tumors of the Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China; 3Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yirong Li, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430061, People’s Republic of China, Tel +8618602718052, Email [email protected]

Background: Staphylococcus aureus (S. aureus) was able to rapidly evolve and adapt under the pressure of antibiotics, host immune and environmental change. After Corona Virus Disease 2019 (COVID-19) epidemic in Wuhan, China, a large number of disinfectants were used, which might result in rapid evolution of S. aureus.
Methods: A total of 619 S. aureus isolates were collected from Zhongnan Hospital, Wuhan University from 2018 to 2021, including group BEFORE (309 strains collected before COVID-19 pandemic) and group AFTER (310 strains collected after COVID-19 pandemic), for comparing the changes of molecular epidemiology. The molecular characteristics of isolates were analyzed by Multi-locus sequence typing (MLST), spa, chromosomal cassette mec (SCCmec) typing, virulence genes were screened by the PCR, antibiotic susceptibility test was carried out by the VITEK system.
Results: Thirty-six sequence types (STs) belonging to 14 clone complexes (CCs) were identified. ST5 was the most prevalent clone in both groups, and ST7, ranking the sixth in group BEFORE, became the second dominant clone in group AFTER (6.5% vs 10.0%), whereas ST239 decreased from the seventh to the fourteenth (5.8% vs 1.9%). ST7 in group AFTER had a higher positive rate of virulence genes, including hlb, fnbB, seb, lukDE, sdrE and the proportion of ST7-t091 MRSA strains increased from 19.1% to 50% compared with group BEFORE. Though no significant difference of MRSA proportion was found between two groups, SCCmec type-III in group AFTER decreased (p< 0.01). Though the rate of multidrug-resistance (MDR) decreased, the virulence genes hlb, hlg, fnbB, seb and pvl carrying rates were significantly elevated in MRSA strains of group AFTER.
Conclusion: After COVID-19 pandemic, ST7 becomes one of the predominant S. aureus clones in Wuhan and the carrying rate of SCCmec and virulence genes is on the rise. Therefore, it is essential to strengthen the surveillance of ST7 S. aureus clone.

Keywords: Staphylococcus aureus, molecular characterization, antimicrobial resistance, virulence gene, disinfectant

Introduction

Staphylococcus aureus (S. aureus), a major human opportunistic pathogen, can cause a variety of infectious diseases including skin and soft-tissue infections, bacteremia, ventilator-associated pneumonia and toxic shock syndrome.1,2 A rapid and proper administration of antibiotics is the most important means to inhibit S. aureus’ growth and prevent disease progression. Under selective pressure of antibiotics, S. aureus can rapidly evolve and adapt with the help of gene mutation or horizontal gene transfer (HGT), leading to the emergence of multidrug-resistance (MDR).3,4 The most notorious MDR S. aureus was Methicillin-resistant Staphylococcus aureus (MRSA), which was first found in the United Kingdom in 1961, two years after the administration of Methicillin. To date, it is still a MDR bacteria puzzling global doctors. MRSA in most cases accounts for at least 25% to 50% of S. aureus infections in hospital settings and mortalities of 33% was reported for MRSA.5,6 MRSA infections are responsible for longer hospital stays, increased hospital costs, and poorer outcomes compared to methicillin-sensitive S. aureus (MSSA) infections.7 Moreover, MRSA clones have been reported to be associated with a certain of molecular type.8–10 ST239-t030, ST5-t2460 and ST59-t437 isolates were most found to be MRSA, whereas ST188-t189 and ST7-t091 isolates were predominant MSSA clones,4,11–13 which suggests that molecular characteristics surveillance contributes to the empirical use of antibiotics in patients with S. aureus infection.

In addition to the selective pressure of antibiotics, host immune system, especially innate immunity system, can encircle and intercept, and finally kill S. aureus, which prevents the progress of infection. Cells involved in innate immunity include neutrophils, monocytes, macrophages, and NK cells, which have specific receptors on their surface, so-called pattern recognition receptors (PRRs), for recognizing bacteria following by the clear of bacteria.14,15 S. aureus consists of a variety of virulent proteins, which promotes the adhesion and invasion to host cells, and the evasion of innate immune responses. Fibronectin-binding protein A (fnbA), fibronectin-binding protein B (fnbB), clumping factor A (clfA) and clumping factor B (clfB) push S. aureus to bind to host cells at the initial stage of infection.16 Cytolytic toxins including hemolysin and Panton-Valentine Leukocidin (pvl) can lyse host cells, causing the release and spread of S. aureus, and even tissue damage.17 More than 70% of S. aureus isolates are exotoxin-producing strains, such as staphylococcal enterotoxins A, B, and C (sea, seb, sec), which can act as superantigens to penetrate the epidermal barrier and exacerbate the inflammatory process.14 Recent studies showed imbalanced cell-mediated immune response was found in severe and critical Coronavirus disease 2019 (COVID-19) patients,18,19 but it was not clear whether the immune imbalance influences on the virulence of S. aureus.

Stress from the environment can also cause S. aureus to adapt and evolve rapidly. Recent studies showed that widely used benzalkonium chloride disinfectants promote antibiotic resistance due to co-selection.20 Studies have shown that diluted or residual disinfectants in the environment can increase bacterial resistance through phenotypic adaptation, genetic mutation and HGT.21 One study reported that high concentration and frequent application of disinfection increase the detection of MRSA infections in psychiatric hospitals during the COVID-19 pandemic.22 And one study indicated that the molecular characteristics of the epidemic strains in Kunming had changed significantly since the COVID-19 epidemic.23 These studies have a common limitation; the sample size is small and type II errors can easily occur. Patients with COVID-19 were firstly identified in Wuhan, and as of March 2020, 2000 tons of disinfectants have been used in this region,24,25 therefore, we collected a total of 619 S. aureus isolates before and after the extensive use of disinfectants in a tertiary hospital in Wuhan, for comparing the changes of molecular typing, antimicrobial resistance and virulence factors.

The molecular characteristics of these isolates were analysed by Multi-locus sequence typing (MLST), spa, SCCmec typing, whereas virulence genes were screened by the PCR assay, and the antibiotic susceptibility tests were carried out by the VITEK system.

Materials and Methods

Bacterial Isolates

A total of 619 non-repetitive S. aureus isolates were collected in Zhongnan Hospital, Wuhan University, during the period from 2018 to 2021, including group BEFORE (309 strains collected before COVID-19 pandemic) and group AFTER (310 strains collected after COVID-19 pandemic). These strains were isolated from sputum, alveolar lavage fluid, pus, wound secretions, blood, urine, catheter tips and other clinical specimens. Repeated strains of the same patient were excluded and only the first isolated strains were included. All isolates were initially identified by colony morphology, gram staining, coagulase tests at the clinical microbiology laboratory, and then MALDI-TOF/MS (VITEK MS, bioMérieux) was used to further confirm. All isolates were stored in Tryptic Soy Broth (TSB) with glycerol at −80°C for later study.

S. aureus DNA Extraction

The stored S. aureus isolates were streaked on blood agar and incubated at 37°C overnight, and a single colony was transferred into 5mL TSB medium and incubated at 37°C overnight at 220 rpm. S. aureus pellets were then suspended in 200 µL of buffer containing 10 µg of lysostaphin (Coolaber, China) at a concentration of 1mg/mL. After incubation at 37°C for 30 minutes, DNA was extracted using a rapid DNA extraction kit (Aidlab, China) according to the manufacturer’s protocol. DNA quantity and purity were determined using the NanoDrop 2000 (Thermo Fisher Scientific, USA). All of the extracted DNAs were stored at −20° for future experiments.

Molecular Typing

Molecular characteristics of all S. aureus isolates were analyzed by Staphylococcal protein A (spa) typing and Multi-locus sequence typing (MLST). The reaction conditions and primers required for PCR were similar to previous study.26 PCR products were then subject to sanger sequencing (Tsingke Biotechnology, China). The resulting sequences were compared with the existing sequences available on the MLST website (http://www.pubmlst.net) for S. aureus, which designated sequence type (ST) for S. aureus. The clone complex (CC) was analyzed through the eBURST. The spa typing was based on variations in the polymorphic X region of the staphylococcal protein A (spa) gene. The X region of each isolate was amplified using PCR and sequenced with DNA sequencing (Tsingke Biotechnology, China). The sequence data of the amplified products were submitted to the website (http://www.spaserver.ridom.de) to obtain the spa type for each isolate.27 Primers used for MLST and spa typing were shown in the Supplementary Table S1. SCCmec is a mobile genetic element, which is the site of insertion and integration of antibiotic resistance genes. S. aureus usually develops resistance to methicillin by acquiring SCCmec elements. A multiplex PCR assay was used to analyze MRSA SCCmec I–V types. Primers and reaction conditions required for PCR, and interpretation of results were as described in the literature.28

Screening for Virulence Factors

All isolates were screened by a conventional PCR assay for the following 18 staphylococcal virulence factors: hemolysin genes (hla, hlb, hld, hlg), adhesion genes (clfA, clfB, fnbA, fnbB), enterotoxin gene (sea, seb, sec), exfoliative gene (eta, etb), Panton-Valentine Leukocidin (pvl), lukED, sdrC, sdrD, sdrE. The annealing temperature and elongation time were determined according to the primer and product length. Some of the virulence gene primers were from the references.4 Primers used for PCR were shown in the Supplementary Table S1.4,16 All PCR products were analyzed by 1.5% agarose gel electrophoresis.

Antimicrobial Susceptibility Testing

The antibiotic susceptibility testing of all isolates in this study was performed on a VITEK system (BioMérieux, Marcy l′ Etoile, France) according to manufacturer’s instructions. Results were interpreted in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines.29 The antibiotics tested in the present study were as follows: levofloxacin (LEV), gentamicin (GEN), ciprofloxacin (CIP), vancomycin (VAN), erythromycin (ERY), clindamycin (CLI), linezolid (LZD), tigecycline (TGC), moxifloxacin (MXF), oxacillin (OXA), quinupristin-dalfopristin (QUD), tetracycline (TET), rifampicin (RIF), penicillin (PEN). The MRSA isolates were further identified using PCR to confirm the presence of the mecA. ATCC 25923 were used as a quality control strain.

Statistical Analysis

All statistical analyses were performed using the IBM SPSS Statistics 25.0. GraphPad Prism 9.0 software was used to plot the experimental data. The virulence gene profiles and antimicrobial susceptibilities were analyzed using two tailed chi-square test or Fisher’s exact test. p<0.05 was considered to be statistically significant.

Results

Clinical Characteristics of S. aureus Isolates

A total of 619 non-repetitive S. aureus isolates were collected from inpatients during the period from 2018 to 2021. Of them, 267 (43.1%) were found to be MRSA and there was no significant difference of MRAS proportion between group BEFORE and group AFTER (42.4% vs 43.9%, p>0.05) (Table 1). There was also no significant difference of patient’s gender, age and specimen source between two groups (Table 1). These isolates were commonly recovered from the male patients rather than the female (62.7% vs 37.3%, p<0.05), most of whom were aged over 20 years old (95.3%, 590/619). In addition, S. aureus were mostly isolated from skin and soft tissue specimens (47.0%, 291/619), followed by respiratory system specimens (26.0%, 161/619), blood (14.7%, 91/619) and other specimen sources (12.3%, 76/619).

Table 1 Specimen Information from Inpatients Infected with S. aureus

Molecular Characteristics of S. aureus Isolates

Among the 619 S. aureus isolates, 36 STs were identified. ST types identified in both groups included ST1, ST188, ST2315, ST5, ST6, ST306, ST7, ST8, ST72, ST239, ST630, ST15, ST1281, ST22, ST25, ST30, ST59, ST88, ST121, ST398. ST9, ST573, ST764, ST845, ST217, ST954, ST4121, ST1163. ST45 and ST5615 were detected only in group BEFORE, whereas ST6159, ST2112, ST5459 ST308, ST7241 and ST946 were found only in group AFTER. The most predominant ST type was ST5 in two groups, followed by ST188, ST22, ST59 and ST398 in group BEFORE, and ST7, ST22, ST188 and ST398 in group AFTER (Figure 1A and Table 2). ST7, ranking the sixth in group BEFORE, was elevated to the second in group AFTER (6.5% vs 10.0%, p>0.05), while ST239 decreased from the seventh to the fourteenth (5.8% vs 1.9%, p<0.05). Fourteen CC types were identified according to eBURST, namely CC1, CC5, CC7, CC8, CC15, CC20, CC22, CC25, CC30, CC45, CC59, CC88, CC121, CC398, and the most prevalent CC was CC5 (26.2%, 162/619). When spa typing and MSLT were combined to analyze, the most prevalent clone was ST5-t2460 (11.0%, 34/309), followed by ST188-t189 (9.1%, 28/309), ST22-t309 (8.1%, 25/309), ST59-t437 (4.9%, 15/309), ST239-t030 (4.9%, 15/309), ST1-t127 (3.9%, 12/309) and ST7-t091 (3.6%, 11/309) in group BEFORE. In group AFTER, the most prevalent clone was also ST5-t2460 (16.1%, 50/310), followed by ST22-t309 (8.7%, 27/310), ST188-t189 (7.7%, 24/310), ST7-t091 (6.5%, 20/310), ST59-t437 (4.2%, 13/310), ST398-t034 (3.9%, 12/310) (Table 2). The proportion of ST7-t091 and ST239-t030 changed obviously, especially ST239-t030 has fallen out of the top ten. There was a strong association between some certain spa types and STs, ST188 was associated with t189 (88.1%, 52/59), ST22 was primarily associated mainly with t309 (88.1%, 52/59), and ST1281 was mainly associated with t164 (82.4%, 14/17) (Table 2). There were four SCCmec types, including type II (37.1%, 99/267), III (8.6%, 23/267), IV (43.8%, 117/267), V (10.5%, 28/267). Type III decreased significantly in group AFTER (13.7% vs 3.7%, p< 0.01) (Figure 1B). Certain association was observed among specific SCCmec, ST and spa types in MRSA isolates. Most ST5-t2460 were MRSA-II isolates, and ST239-t030 were MRSA-III isolates, whereas most ST188-t189, ST6-t701 and ST1281-t164 were MSSA isolates. In addition, most ST7-t091 in group BEFORE were MSSA (81.9%, 9/11), while half of ST7-t091 in group AFTER were MRSA isolates (50%, 10/20), and there was no significant difference of MRSA proportion in ST7-t091clone between two groups (p > 0.05). ST22-t309 was considered as the main MSSA isolate type in previous reports,4,30,31 but MRSA accounted for 67.3% (35/52) of the isolates in this study (Table 2).

Table 2 Molecular Characteristics of S. aureus Isolates

Figure 1 Distribution in Sequence Types (STs) of Staphylococcus aureus isolates between group BEFORE and group AFTER (A). SCCmec typing of MRSA isolates between group BEFORE and group AFTER (B). *p < 0.05, **p < 0.01.

Antimicrobial Resistance

The results of antibiotic susceptibility testing showed in Figure 2. All of isolates were susceptible to VAN, TGC and QUD, whereas the majority of these strains were resistant to PEN (93.4%, 578/619). The resistance rates to remaining antibiotics ranged from 0.2% to 61.5%. There was no significant difference in the resistance rate to tested antibiotics except RIF between two groups (Figure 2A). The antimicrobial resistance rate to LEV, CIP, MXF and RIF decreased significantly in MRSA strains of group AFTER as well as the prevalence of MDR (77.1%, 65.4%, p< 0.05) (Figure 2B). In addition, MRSA isolates had higher resistance rates to most antibiotics and MDR rate than MSSA isolates (Figure 2B and C). Three representative MRSA clones including ST5-II/t2460, ST22-IV/t309 and ST239-III/t030 were selected for further analyzing antimicrobial resistance profiles (ARPs) to 6 non-beta-lactam antibiotics. ARPs included antimicrobial agents which more than 70% MRSA isolates were resistant.32 It was found that antibiotics GEN was included in the APRs of ST5-II/t2460 clone of group AFTER rather group BEFORE (Table 3).

Table 3 Antimicrobial Resistance Profiles (APRs) of Some Major MRSA Clones

Figure 2 The antimicrobial resistance among BEFORE S. aureus isolates were compared with those AFTER S. aureus isolates (A). The antimicrobial resistance among BEFORE MRSA isolates were compared with those AFTER MRSA isolates (B). The antimicrobial resistance among BEFORE MSSA isolates were compared with those AFTER MSSA isolates (C). *p < 0.05, ****p < 0.0001.

Abbreviation: MSSA, Methicillin-sensitiveStaphylococcus aureus.

Virulence Gene Profiles

All isolates contained five detected virulence genes at least, and 97.6% (604/619) isolates have seven or more tested virulence genes. The frequencies of virulence genes among S. aureus, MRSA and MSSA isolates in the two groups were shown in Supplementary Table S2. ST22-t309 had a pvl carrying rate of 96.2%, while ST7-t091 had a pvl carrying rate of only 25.8%. The carrying rates of some hemolysin genes and adhesins were also different among different types of S. aureus (Table 4). In addition, the virulence genes hlb, fnbB, seb, lukDE, sdrE were found to be significantly higher in ST7 clone of group AFTER (Table 5).

Table 4 Carrying Rates of Virulence Genes in Main ST-Spa Isolates

Table 5 The Frequencies of Virulence Genes Between ST7 and ST239

Discussion

S. aureus can invade different organs and systems, causing a wide range of infections, from mild skin and soft tissue infections to life-threatening diseases including infective endocarditis, bacteremia and sepsis.33 Although the antimicrobial resistance rate of MRSA strains has declined in some countries and regions in recent years, MRSA is still an important pathogen of community and health-care-related infections.34,35 Studies have shown that diluted or residual disinfectants in the environment can increase bacterial resistance and resistance through phenotypic adaptation, genetic mutation, and horizontal gene transfer (HGT).21 One study reported that high concentration and frequent application of disinfection increase the detection of MRSA infections in psychiatric hospitals during the COVID-19 pandemic.22 However, in the present study, it was shown that there was no significant difference of the resistance rate to each antibiotic between group BEFORE and group AFTER as well as MRSA proportion, which was not consistent to the previous study and need to be studied intensively. The antimicrobial resistance rate to LEV, CIP, MXF and RIF decreased significantly in MRSA strains of group AFTER as well as the prevalence of MDR and GEN was included in the APRs of ST5-II/t2460 clone of group AFTER. These changes in antibiotic sensitivity and resistance information can guide clinical selection of antibiotics in the area.

Molecular typing showed that ST5-t2460 was the most common S aureus clone, followed by ST188-t189, ST22-t309, ST59-t437 and ST239-t030 before COVID-19 pandemic in Wuhan. After COVID-19 pandemic, the most frequent type was still ST5-t2460, following by ST22-t309, ST188-t189, ST7-t091 and ST59-t437. An obvious change was that ST239-t030 was not only replace by ST7-t091 in the top five S aureus clones, but also fall out of the top ten after COVID-19 pandemic. In our previous studies during the period from 2017 to 2018, ST239-t030 was found to rank second to ST5-t2460,4,36 which indicating that ST239-t030 clone decreased rapidly in the last four years, and to date, was not one of the most prevalent clones in S. aureus isolates in Wuhan. Supporting our result, ST239-t030 was found to significantly decreased from 20.3% to 1% during the period from 2008 to 2017.35 As the predominant healthcare-associated MRSA (HA-MRSA) clones, ST239 infections are transmitted mainly through hand contact,35,37 therefore, it is reasonable to speculate that due to the use of large quantities of disinfectants and greater attention to hand disinfection and personal protection during the COVID-19 pandemic, ST239-t030 clones may be less adaptable and competitive when faced with highly selective pressures in health-care settings, which probably lead to the reduction of ST239-t030. An article reported that the dominant molecular type was ST22-t309 in 2019 and 2021, while in 2020, it was ST59-t437 in Kunming.23 These changes suggest that the possible impact of disinfectant use during the COVID-19 pandemic on the evolution of S. aureus.

It is another important to point that ST7 isolates show an increasing trend and becomes the second dominant strain after COVID-19 pandemic. One previous study reported ST7 as the predominant clone in S. aureus skin and soft tissue infections isolates from Wenzhou, China, and this clone was rarely found in Chinese isolates before.38 In our previous study in 2018, although ST7 was found to be one of the most dominant clone, which was found to rank second to ST5, ST239, ST59, and ST188, and associated with MSSA.36 In the present study, three main subclones were identified and ST7-t091 was the predominant. The MRSA proportion of ST7-t091 increased from 19.1% (before COVID-19 pandemic) to 50% (after COVID-19 pandemic). Moreover, ST7 clone of group AFTER had a higher positive rate of a variety of virulence genes, including hlb, fnbB, seb, lukDE, sdrE. These data indicating ST7 isolates have a strong ability to acquire SCCmec element and virulence genes under the pressure of disinfectant agent, which in part interpreted why ST7 became a common S. aureus clone after pandemic. A recent study revealed that ST7 was the main reported genotype of S. aureus in wholesale and retail pork in Wuhan (detection rate 57.5%) and the results reveal new potential threats to food safety and public health from wholesale and retail pork.39 In addition, ST22 clone, a community-associated S. aureus, was found to be the main MSSA isolate type in Wuhan in our previous reports,4 but 67.3% ST22 clones presented with resistance to methicillin in this study, which reminds us to alert that ST22 has the potential to be one of the most common MRSA strains in the next few years.

It is well known that S. aureus is notorious for its ability to produce a series of virulence factors.40 Previous studies have shown that pvl is closely related to the prognosis and mortality of infected patients. Among patients with S. aureus pneumonia, the survival rate at 48 hours after admission was 63% for pvl-positive patients and 94% for pvl-negative patients.41,42 Specific molecular typing was associated with virulence genes. For example, ST22-t309 had a pvl carrying rate of 96.2%, while ST7-t091 had a pvl carrying rate of only 25.8%. The carrying rates of some hemolysin genes and adhesins were also different among different types of S. aureus. Furthermore, the rate of pvl in this study, was significantly higher than the previous detection rate in this area (48.6% vs 18.9%, p<0.001),4 and moreover, S. aureus isolates collected after pandemic had higher positive rate of the pvl than those before pandemic. Therefore, we should attach great importance to the relationship between the change of molecular prevalence of S. aureus and the virulence gene carrying rate. The limitation should be acknowledged was that our results were from a single center, which may affect the representativeness of the samples to this study. These changes and limitation remind that more isolates for longer period should be collected and analysed to show how S. aureus has evolved and adapted rapidly to this stressful environment.

Conclusion

In conclusion, before and after the epidemic, the molecular typing, antimicrobial resistance and virulence of S. aureus have changed. ST5-t2460 is still the most common clone in the region and ST22-t309 had a pvl carrying rate of 96.2%. ST7 becomes the second dominant clone after COVID-19 pandemic with an increasing trend of both carrying SCCmec and more virulent genes in Wuhan. CC/ST/spa typing was closely related to antimicrobial resistance and virulence genes of S. aureus. So, more isolates for longer period should be collected to detect changes in the prevalence of this important pathogen.

Data Sharing Statement

Data sets used and analyzed in the current study are included in this published article.

Ethics Approval and Consent to Participate

This study did not involve patient data and only used anonymous clinical residue samples from routine laboratory tests in hospital and was approved by the Zhongnan hospital of Wuhan university.

Consent for Publication

All authors approved the final manuscript and gave consent for publication.

Acknowledgments

The authors thank all the colleagues and the reviewers who helped with this work.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for the contents of the article.

Funding

This study was supported by the National Natural Science Foundation of China (NO. 82172333); Key Research and Development Program of Hubei Province (2022BCA019); 2021 Hubei Provincial Leading Public Health Talents Project (WSJKRC2022012); Establishment of accurate etiological diagnosis strategy for severely infected children (2021YFC2701803).

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships.

References

1. Cheung GYC, Bae JS, Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence. 2021;12(1):547–569.

2. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007;298(15):1763–1771.

3. Manara S, Pasolli E, Dolce D, et al. Whole-genome epidemiology, characterisation, and phylogenetic reconstruction of Staphylococcus aureus strains in a paediatric hospital. Genome Med. 2018;10(1):82.

4. Xiong M, Zhao J, Huang T, et al. Molecular characteristics, virulence gene and wall teichoic acid glycosyltransferase profiles of Staphylococcus aureus: a multicenter study in China. Front Microbiol. 2020;11:2013.

5. Lakhundi S, Zhang K. Methicillin-resistant Staphylococcus aureus: molecular characterization, evolution, and epidemiology. Clin Microbiol Rev. 2018;31(4):e00020–18.

6. Wolk DM, Struelens MJ, Pancholi P, et al. Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays. J Clin Microbiol. 2009;47(3):823–826.

7. Fortuin-de Smidt MC, Singh-Moodley A, Badat R, et al. Staphylococcus aureus bacteraemia in Gauteng academic hospitals, South Africa. Int J Infect Dis. 2015;30:41–48.

8. Peacock SJ, Paterson GK. Mechanisms of methicillin resistance in Staphylococcus aureus. Annu Rev Biochem. 2015;84:577–601.

9. Barber M. Methicillin-resistant staphylococci. J Clin Pathol. 1961;14(4):385–393.

10. Cuny C, Friedrich A, Kozytska S, et al. Emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different animal species. Int J Med Microbiol. 2010;300(2–3):109–117.

11. Geng W, Qi Y, Li W, et al. Epidemiology of Staphylococcus aureus in neonates on admission to a Chinese neonatal intensive care unit. PLoS One. 2020;15(2):e0211845.

12. Liao F, Gu W, Yang Z, et al. Molecular characteristics of Staphylococcus aureus isolates from food surveillance in southwest China. BMC Microbiol. 2018;18(1):91.

13. Li X, Fang F, Zhao J, et al. Molecular characteristics and virulence gene profiles of Staphylococcus aureus causing bloodstream infection. Braz J Infect Dis. 2018;22(6):487–494.

14. Nowicka D, Grywalska E. Staphylococcus aureus and host immunity in recurrent furunculosis. Dermatology. 2019;235(4):295–305.

15. Ruiz AL, Soudja SM, Deceneux C, Lauvau G, Marie JC. NK1.1+ CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response. Nat Commun. 2014;5:5150.

16. Ashraf S, Cheng J, Zhao X. Clumping factor A of Staphylococcus aureus interacts with AnnexinA2 on mammary epithelial cells. Sci Rep. 2017;7:40608.

17. Melles DC, Gorkink RF, Boelens HA, et al. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus. J Clin Invest. 2004;114(12):1732–1740.

18. Wang J, Li Q, Qiu Y, Lu H. COVID-19: imbalanced cell-mediated immune response drives to immunopathology. Emerg Microbes Infect. 2022;11(1):2393–2404.

19. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718–724.

20. Mc Carlie S, Boucher CE, Bragg RR. Molecular basis of bacterial disinfectant resistance. Drug Resist Updat. 2020;48:100672.

21. Tong C, Hu H, Chen G, Li Z, Li A, Zhang J. Disinfectant resistance in bacteria: mechanisms, spread, and resolution strategies. Environ Res. 2021;195:110897.

22. Yang M, Feng Y, Yuan L, Zhao H, Gao S, Li Z. High concentration and frequent application of disinfection increase the detection of methicillin-resistant staphylococcus aureus infections in psychiatric hospitals during the COVID-19 pandemic. Front Med. 2021;8:722219.

23. Ma M, Tao L, Li X, et al. Changes in molecular characteristics and antimicrobial resistance of invasive Staphylococcus aureus infection strains isolated from children in Kunming, China during the COVID-19 epidemic. Front Microbiol. 2022;13:944078.

24. Zhang H, Tang W, Chen Y, Yin W. Disinfection threatens aquatic ecosystems. Science. 2020;368(6487):146–147.

25. Chen Z, Guo J, Jiang Y, Shao Y. High concentration and high dose of disinfectants and antibiotics used during the COVID-19 pandemic threaten human health. Environ Sci Eur. 2021;33(1):11.

26. Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000;38(3):1008–1015.

27. Koreen L, Ramaswamy SV, Graviss EA, Naidich S, Musser JM, Kreiswirth BN. Spa typing method for discriminating among Staphylococcus aureus isolates: implications for use of a single marker to detect genetic micro- and macrovariation. J Clin Microbiol. 2004;42(2):792–799.

28. Boye K, Bartels MD, Andersen IS, Møller JA, Westh H. A new multiplex PCR for easy screening of methicillin-resistant Staphylococcus aureus SCCmec types I-V. Clin Microbiol Infect. 2007;13(7):725–727.

29. Wayne P. Performance Standards for Antimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute CLSI; 2018.

30. Zhou W, Jin Y, Liu X, Chen Y, Shen P, Xiao Y. Comparison of genetic features and evolution of global and Chinese strains of community-associated methicillin-resistant Staphylococcus aureus ST22. Microbiol Spectr. 2022;10(1):e0203721.

31. Xiao N, Yang J, Duan N, Lu B, Wang L. Community-associated Staphylococcus aureus PVL(+) ST22 predominates in skin and soft tissue infections in Beijing, China. Infect Drug Resist. 2019;12:2495–2503.

32. Kong H, Yu F, Zhang W, Li X, Wang H. Molecular epidemiology and antibiotic resistance profiles of methicillin-resistant Staphylococcus aureus strains in a Tertiary Hospital in China. Front Microbiol. 2017;8:838.

33. Demir T, Coplu N, Esen B. Comparative analysis of phenotypic and genotypic detection of methicillin resistance among Staphylococcus aureus. Indian J Pathol Microbiol. 2016;59(3):314–317.

34. Prabaker K, Weinstein RA. Trends in antimicrobial resistance in intensive care units in the United States. Curr Opin Crit Care. 2011;17(5):472–479.

35. Dai Y, Liu J, Guo W, et al. Decreasing methicillin-resistant Staphylococcus aureus (MRSA) infections is attributable to the disappearance of predominant MRSA ST239 clones, Shanghai, 2008–2017. Emerg Microbes Infect. 2019;8(1):471–478.

36. Fu Y, Xiong M, Li X, et al. Molecular characteristics, antimicrobial resistance and virulence gene profiles of Staphylococcus aureus isolates from Wuhan, Central China. Infect Drug Resist. 2020;13:2063–2072.

37. Pittet D, Hugonnet S, Harbarth S, et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Infection Control Programme. Lancet. 2000;356(9238):1307–1312.

38. Yu F, Liu Y, Lv J, et al. Antimicrobial susceptibility, virulence determinant carriage and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections. Braz J Infect Dis. 2015;19(6):614–622.

39. Zhu Z, Liu X, Chen X, et al. Prevalence and virulence determinants of Staphylococcus aureus in wholesale and Retail Pork in Wuhan, Central China. Foods. 2022;11(24):4114.

40. Peng H, Liu D, Ma Y, Gao W. Comparison of community- and healthcare-associated methicillin-resistant Staphylococcus aureus isolates at a Chinese tertiary hospital, 2012–2017. Sci Rep. 2018;8(1):17916.

41. Genestier AL, Michallet MC, Prévost G, et al. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J Clin Invest. 2005;115(11):3117–3127.

42. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002;359(9308):753–759.

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