, a major human pathogen, has a collection of virulence factors and the ability to acquire resistance to most antibiotics. This ability is further augmented by constant emergence of new clones, ...making
a "superbug." Clinical use of methicillin has led to the appearance of methicillin-resistant
(MRSA). The past few decades have witnessed the existence of new MRSA clones. Unlike traditional MRSA residing in hospitals, the new clones can invade community settings and infect people without predisposing risk factors. This evolution continues with the buildup of the MRSA reservoir in companion and food animals. This review focuses on imparting a better understanding of MRSA evolution and its molecular characterization and epidemiology. We first describe the origin of MRSA, with emphasis on the diverse nature of staphylococcal cassette chromosome
(SCC
).
and its new homologues (
,
, and
), SCC
types (13 SCC
types have been discovered to date), and their classification criteria are discussed. The review then describes various typing methods applied to study the molecular epidemiology and evolutionary nature of MRSA. Starting with the historical methods and continuing to the advanced whole-genome approaches, typing of collections of MRSA has shed light on the origin, spread, and evolutionary pathways of MRSA clones.
Phylogenetic analysis based on single-nucleotide polymorphism (SNP)-based through whole-genome sequencing is recognized as the standard method for probing nosocomial transmission. However, the ...application of WGS is constrained by the high cost of equipment and the need for diverse analysis tools, which limits its widespread use in clinical laboratory settings. In Japan, the prevalent use of PCR-based open reading frame typing (POT) for tracing methicillin-resistant Staphylococcus aureus (MRSA) transmission routes is attributed to its simplicity and ease of use. Although POT's discriminatory power is considered insufficient for nosocomial transmission analysis, conclusive data supporting this notion is lacking. This study assessed the discriminatory capabilities of SNP analysis and POT across 64 clinical MRSA strains. All 21 MRSA strains of ST5/SCCmec IIa, having more than 16 SNPs, demonstrated distinct clones. Conversely, two strains shared the same POT number and were identified as group A. Among the 12 MRSA strains of ST8/SCCmec IVl with over nine SNPs, five fell into POT group B, and five into POT group C. All four MRSA strains of ST8/SCCmec IVa were classified into POT group D, although they included strains with more than 30 SNPs. Among the 27 MRSA strains of ST1/SCCmec IVa, 14 were classified into POT group E. However, except for two clusters (each comprising two or three strains), all had SNP counts >10 (Fig. 1-D). SNP analysis of MRSA in CC1/SCCmec IV showed that several strains had the same number of SNPs in POT number (106-183-37), even among bacteria with >100 SNPs, indicating POT's limited use in detailed nosocomial transmission analysis.
Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases infection risk in both patients and healthy individuals. Decolonization therapy has been proven to reduce S. aureus ...infections, but data on the effectiveness of individual decolonization strategies in community-onset MRSA carriage are scarce.
The aim of this narrative review was to summarize the evidence on strategies for the elimination of MRSA colonization in community-onset MRSA carriers.
PubMed database was searched for studies on MRSA eradication, from inception to July 2023.
Topical therapy is proven to be effective in nasal-only carriage and in temporary load reduction. Mupirocin nasal ointment in combination with chlorhexidine body wash is highly effective in nasal-only MRSA carriers in the community as well. In patients with extra-nasal colonization, addition of orally administered antibiotics likely increases success rates compared with topical therapy alone. Studies on systemic treatment of extra-nasal MRSA decolonization are subject to a high heterogeneity of antimicrobial agents, treatment duration, and control groups. The majority of evidence supports the use of a combination of topical therapy with rifampin and another antimicrobial agent. Decolonization treatment with probiotics is a promising novel non-antibiotic strategy. However, achieving long-term decolonization is more likely in countries with low MRSA prevalence, given the risk of recolonization in a context of high MRSA prevalence.
The decision to pursue community-onset MRSA eradication treatment in the individual patient should be based on the combination of the treatment objective (short-term bacterial load reduction in health care settings vs. long-term eradication in community settings), and the likelihood of successful decolonization. The latter is influenced by both individual risk factors for treatment failure, and the risk of recolonization. The addition of a combination of systemic antibiotics is rational for extra-nasal long-term decolonization. To determine the most effective systemic antimicrobial agents in MRSA decolonization, more research is needed.
The healthcare burden rendered by methicillin-resistant Staphylococcus aureus (MRSA) warrants the development of therapeutics that offer a distinct benefit in the clinics as compared to conventional ...antibiotics. The present study describes the potential of napthalimide-based synthetic ligands (C1-C3) as inhibitors of the staphylococcal nuclease known as micrococcal nuclease (MNase), a key virulence factor of the pathogen. Amongst the ligands, the most potent MNase inhibitor C1 rendered non-competitive inhibition, reduced MNase turnover number (Kcat) and catalytic efficiency (Kcat/Km) with an IC50 value of ~950 nM. CD spectroscopy suggested distortion of MNase conformation in presence of C1. Flow cytometry and confocal microscopy indicated that C1 restored the ability of activated THP-1 cells to engulf DNA-entrapped MRSA cells. Interestingly, C1 could inhibit MRSA adhesion onto collagen. For potential application, C1-loaded pluronic F-127 micellar nanocarrier (C1-PMC) was generated, wherein the anti-adhesion activity of the pluronic carrier (PMC) and C1 was harnessed in tandem to deter MRSA cell adhesion onto collagen. MRSA biofilm formation was hindered on C1-PMC-coated titanium (Ti) wire, while eluates from C1-PMC-coated Ti wires were non-toxic to HEK 293, MG-63 and THP-1 cells. The multifunctional C1 provides a blueprint for designing therapeutic materials that hold translational potential for mitigation of MRSA infections.
The nematode Caenorhabditis elegans has recently been developed as a host model for the study of Staphylococcus aureus virulence and pathogenesis. Here, the toxicity and virulence of representative ...clinical isolates of our methicillin-resistant S. aureus (MRSA) epidemic strains were studied using this model. The strains USA300 (associated with community infection outbreaks), USA400 (associated with sporadic community infections) and CMRSA2 (associated with both hospital and community infections), as well as the nematocidal reference strain NCTC8325, showed high nematocidal activity, both by killing the majority of the nematodes (> 90%) over 9 days, and by inhibiting second-generation nematode growth. By contrast, the typical hospital-associated MRSA strain CMRSA6, the colonization strain M92, and the non-pathogenic Staphylococcus epidermidis control strain ATCC12228 were non-toxic to the nematode, which behaved normally. The absence of nematocidal activity does not reflect lack of growth or reduced growth of the bacterial inoculum. The two non-nematocidal strains share similar genomic backgrounds, bacterial growth curve patterns and virulence gene profiles. However, the nematocidal strains each showed the same low maximum density growth curve patterns, but possessed distinct genetic profiles; no common virulence gene patterns or specific genes have been elucidated. Our findings demonstrate that community-associated MRSA strains are more pathogenic than hospital-associated MRSA in the C. elegans model and support the use of this model for studying the virulence of S. aureus strains.
I report a rare case of peritonitis caused by bile leakage. A 79-year-old woman underwent ileocecal resection for perforated appendicitis. Postoperatively, she developed sepsis due to a central ...venous catheter infection, but was discharged after the condition responded favorably to catheter removal. The CV tip culture grew MRSA. On the 5th day after discharge, the patient presented to our outpatient clinic with low back pain, abdominal pain and a low-grade fever. Abdominal computed tomography revealed acute cholecystitis with an abdominal wall abscess. Surgery was performed on the following day. At operation, a large volume of bilious ascites was observed in the peritoneal cavity, the gallbladder was necrotic, and its wall was thinned, although there was no obvious perforation. Therefore, cholecystectomy and intraperitoneal drainage were performed. Ascitic fluid culture grew MRSA. Postoperatively, the patient developed MRSA pneumonia, which resolved after vancomycin treatment. The low back pain persisted and further detailed examination revealed pyogenic spondylitis and discitis. Remission was achieved with conservative management, including rest to the affected part and administration of vancomycin and linezolid. Herein, I have reported a case of biliary peritonitis caused by bile leakage secondary to necrotic acalculous cholecystitis associated with MRSA sepsis.
Even though antibiotic resistance in bacteria is a natural phenomenon, the alarming increase in pathogenic bacteria refractory to a wide range of antimicrobials is attracting attention worldwide. ...Indeed, the World Health Organization (WHO) has recently published a list of priority pathogens for which new antimicrobial alternatives are urgently needed. Among these pathogens, methicillin-resistant
(MRSA) strains are perhaps the best known by the general public. In addition to its potential to acquire antibiotic resistance,
can produce a large number of virulence factors, such as hemolysins, enterotoxins, and proteases, and exhibits the ability to form biofilms as well as to evolve into different clones that can spread and colonize new environments. This review provides a brief overview of the latest options in antibacterial therapies, mainly focusing on phage therapy. In this regard, the current stage of research about antimicrobial compounds based on bacteriophages and endolysins against MRSA infections is shown and discussed.
Aims
To determine the Staphylococcus aureus carriage rate in wild mammals in Aragon, northern Spain, to analyse their antimicrobial resistance phenotype/genotype and to characterize the recovered ...isolates.
Methods and Results
Nasal and rectal swabs of 103 mammals were collected in Aragón during the period 2012–2015. Antimicrobial susceptibility, the presence of antimicrobial resistance genes and virulence factors were investigated. Molecular characterization was carried out by spa, MLST, agr and SCCmec. Staphylococcus aureus were recovered from 23 animals (22%). Four of the 23 S. aureus were methicillin‐resistant S. aureus (MRSA). Three MRSA were mecC‐positive and were isolated from European rabbits and were typed as t843 (ascribed to CC130). The remaining MRSA was a mecA‐carrying isolate from European hedgehog, typed as ST1‐t386‐SCCmecIVa‐agrIII and it harboured the blaZ, erm(C), ant(6)‐Ia and aph(3´)‐IIIa resistance genes. A high diversity of spa‐types was detected among the 19 methicillin‐susceptible S. aureus isolates, which showed high susceptibility to the antimicrobials tested. The tst gene and different combinations of staphylococcal enterotoxins were found.
Conclusions
Staphylococcus aureus were detected in nasal and rectal samples of wild mammals. Wild rabbits could be a reservoir of mecC‐MRSA.
Significance and Impact of the Study
This work provides information on the presence and characteristics of S. aureus from mammals in a defined geographic region in Spain.
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