scholarly journals Flavone Markedly Affects Phenotypic Expression of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus Strains Isolated Clinically

2003 ◽  
Vol 26 (10) ◽  
pp. 1478-1483 ◽  
Author(s):  
Hirofumi Shibata ◽  
Chikako Shirakata ◽  
Hiromi Kawasaki ◽  
Yoichi Sato ◽  
Tomomi Kuwahara ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Phenotypic Expression ◽  
Beta Lactam ◽  
Methicillin Resistant

scholarly journals Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Maria Pardos de la Gandara ◽  
Vitor Borges ◽  
Marilyn Chung ◽  
Catarina Milheiriço ◽  
João Paulo Gomes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Phenotypic Expression ◽  
Beta Lactam ◽  
Genetic Determinants ◽  
Methicillin Resistant ◽  
Content Type ◽  
Clonal Type ◽  
Oxacillin Resistance ◽  
Resistant Phenotype ◽  
Six Genes

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA - or a mecC -mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest “archaic” clone of MRSA and in the mecC -carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes ( fruB , gmk , hpt , purB , prsA , and relA ), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.

scholarly journals Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 60 (4) ◽  
pp. 2311-2317 ◽  
Author(s):  
Sandra Aedo ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Response ◽  
Phenotypic Expression ◽  
Beta Lactam ◽  
Resistance Level ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistance Phenotype ◽  
Oxacillin Resistance ◽  
The Impact

ABSTRACTResistance to beta-lactam antibiotics in methicillin-resistantStaphylococcus aureus(MRSA) requires the presence of an acquired genetic determinant,mecAormecC, which encode penicillin-binding protein PBP2A or PBP2A′, respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation ofmecAin the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2andblaI/blaR1) formecAtranscription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a “foreign” determinant such asmecA, as opposed to resistance based on mutations in the nativeS. aureusdeterminantpbpB(encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that theStaphylococcus sciuri pbpDgene (also calledmecAI), the putative evolutionary precursor ofmecA, confers oxacillin resistance in anS. aureusstrain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria.

scholarly journals Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania

2021 ◽  
Author(s):  
Joel Manyahi ◽  
Sabrina J. Moyo ◽  
Said Aboud ◽  
Nina Langeland ◽  
Bjørn Blomberg
Keyword(s):  
Staphylococcus Aureus ◽  
Hiv Infection ◽  
Diffusion Method ◽  
Molecular Characteristics ◽  
People Living With Hiv ◽  
Newly Diagnosed ◽  
Beta Lactam ◽  
Disk Diffusion Method ◽  
Methicillin Resistant ◽  
Inducible Clindamycin Resistance

AbstractDifficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

scholarly journals Novel Combinations of Vancomycin plus Ceftaroline or Oxacillin against Methicillin-Resistant Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA

2013 ◽  
Vol 57 (5) ◽  
pp. 2376-2379 ◽  
Author(s):  
B. J. Werth ◽  
C. Vidaillac ◽  
K. P. Murray ◽  
K. L. Newton ◽  
G. Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Inverse Correlation ◽  
Fluorescent Dye ◽  
Beta Lactam ◽  
Significant Inverse Correlation ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Wall Interactions

ABSTRACTWe demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediateStaphylococcus aureus(VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrrometheneboron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

Protein expression profiles in methicillin-resistant Staphylococcus aureus (MRSA) under effects of subminimal inhibitory concentrations of imipenem

2019 ◽  
Vol 366 (15) ◽  
Author(s):  
Jichun Wang ◽  
Junrui Wang ◽  
Yanyan Wang ◽  
Peng Sun ◽  
Xiaohui Zou ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cellular Proliferation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Expression Profiles ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Methicillin Resistant

ABSTRACT Imipenem is a beta-lactam antibiotic mainly active against gram-negative bacterial pathogens and also could cause cell wall impairment in methicillin-resistant Staphylococcus aureus(MRSA). However, related antibacterial mechanisms of imipenem on MRSA and mixed infections of MRSA and gram-negative bacteria are relatively poorly revealed. This study was to identify proteins in the MRSA response to subminimal inhibitory concentrations (sub-MICs) of imipenem treatment. Our results showed that 240 and 58 different expression proteins (DEPs) in sub-MICs imipenem-treated S3 (a standard MRSA strain) and S23 (a clinical MRSA strain) strains were identified through the isobaric tag for relative and absolute quantitation method when compared with untreated S3 and S23 strains, respectively, which was further confirmed by multiple reactions monitoring. Our result also demonstrated that expressions of multiple DEPs involved in cellular proliferation, metabolism and virulence were significantly changed in S3 and S23 strains, which was proved by gene ontology annotations and qPCR analysis. Further, transmission electron microscopy and scanning electron microscopy analysis showed cell wall deficiency, cell lysis and abnormal nuclear mitosis on S23 strain. Our study provides important information for understanding the antibacterial mechanisms of imipenem on MRSA and for better usage of imipenem on patients co-infected with MRSA and other multidrug-resistant gram-negative bacteria.

scholarly journals Full-Genome Sequencing Identifies in the Genetic Background Several Determinants That Modulate the Resistance Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Carrying the Novel mecC Gene

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Genetic Background ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistance Phenotype ◽  
Beta Lactam Antibiotics ◽  
Oxacillin Resistance ◽  
Mrsa Strains

ABSTRACT Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.

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