Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review

Liu, Wan-Ting; Chen, En-Zhong; Yang, Ling; Chen, Peng; Wang, Qun; Xu, Zhenbo; Chen, Dingqiang

doi:10.1016/j.micpath.2021.104915

Cited by 83 publications

(74 citation statements)

References 77 publications

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“…The most common anti-MRSA antibiotics are vancomycin, daptomycin, ceftaroline, and linezolid. However, their frequent use has accelerated drug resistance development even against those antibiotics [28]. As a conclusion, phage Sb-1 alone already has a proven record for the treatment of S. aureus infections in humans [23].…”

Section: Resultsmentioning

confidence: 99%

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus

et al. 2021

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Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen responsible for not only a number of difficult-to-treat hospital-acquired infections, but also for infections that are community- or livestock-acquired. The increasing lack of efficient antibiotics has renewed the interest in lytic bacteriophages (briefly phages) as additional antimicrobials against multi-drug resistant bacteria, including MRSA. The aim of this study was to test the hypothesis that a combination of the well-known and strictly lytic S. aureus phage Sb-1 and oxacillin, which as sole agent is ineffective against MRSA, exerts a significantly stronger bacterial reduction than either antimicrobial alone. Eighteen different MRSA isolates and, for comparison, five MSSA and four reference strains were included in this study. The bacteria were challenged with a combination of varying dosages of the phage and the antibiotic in liquid medium using five different antibiotic levels and four different viral titers (i.e., multiplicity of infections (MOIs) ranging from 10−5 to 10). The dynamics of the cell density changes were determined via time-kill assays over 16 h. Positive interactions between both antimicrobials in the form of facilitation, additive effects, or synergism were observed for most S. aureus isolates. These enhanced antibacterial effects were robust with phage MOIs of 10−1 and 10 irrespective of the antibiotic concentrations, ranging from 5 to 100 µg/mL. Neutral effects between both antimicrobials were seen only with few isolates. Importantly, antagonism was a rare exception. As a conclusion, phage Sb-1 and oxacillin constitute a robust heterologous antimicrobial pair which extends the efficacy of a phage-only approach for controlling MRSA.

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Section: Resultsmentioning

confidence: 99%

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus

et al. 2021

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“…Strains harboring a D239L, S225R, N146K substitution or a 259–260 insertion in PBP2A had ceftobiprole MICs of 4–8 mg/L [ 73 , 74 ]. Amino acid substitutions in the PBP2A protein such as L357I, E447K, I563T, and S649A in the BND (penicillin-binding domain) and substitutions N104K, V117I, N146K and A228V located outside the BND have also been shown to be responsible for ceftaroline resistance in MRSA strains [ 75 , 76 ]. Breakpoint of resistance to ceftaroline is MIC > 1 mg/L (pneumonia) and MIC > 2 mg/L (other than pneumonia) according to EUCAST [ 14 ] and MIC ≥ 8 mg/L according to CLSI [ 17 ].…”

Section: Resistance To Beta-lactam Antibioticsmentioning

confidence: 99%

“…Substitutions in VraS (S329L), MsrR (E146K), GraR (N197S), RpoB (H481Y or N), Fdh2 (A297V) proteins have been shown to be closely related to vancomycin resistance of VISA strains [ 88 ]. The accumulation of mutations in genes encoding binary regulatory systems such as WalKR (sensor protein kinase/regulator), GraSR (glycopeptide resistance-associated sensor/regulator), and VraSR (vancomycin resistance associated sensor/regulator) plays a major role in the formation of hVISA/VISA strains [ 75 ].…”

Section: Resistance To Glycopeptides and Lipoglycopeptidesmentioning

confidence: 99%

Molecular Mechanisms of Drug Resistance in Staphylococcus aureus

Młynarczyk-Bonikowska

Kowaléwski

Krolak-Ulinska³

et al. 2022

IJMS

146

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This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.

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“…It is believed that its mechanism of action differs from that of other AMPs since daptomycin causes bacterial membrane depolarization rather than membrane disruption and pore formation [ 172 ]. In recent years, resistance in Staphylococcus aureus has been more and more frequently reported, and the search for substitutes that might prolong the clinical use of this important antibiotic is actively underway [ 173 ].…”

Section: Amps—goods Vs Bads and The Long Way Towards Clinical Applicationmentioning

confidence: 99%

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Vanzolini

Bruschi

Rinaldi

et al. 2022

IJMS

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Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.

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Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review

Cited by 83 publications

References 77 publications

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus

Molecular Mechanisms of Drug Resistance in Staphylococcus aureus

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

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