PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Methicillin-Resistant Staphylococcus aureus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1979

Comparative in vitro activity of LY 127935 (6059-S), seven cephalosporins, three aminoglycosides, carbenicillin, and ticarcillin.

LY 127935 (6059-S), a new semi-synthetic beta-lactam antibiotic was tested simultaneously with 6 cephalosporins, 3 aminoglycosides, carbenicillin and ticarcillin against 398 clinical isolates of Gram-negative bacilli and Gram-positive cocci. Many of the organisms were selected for study because of known resistance to one or more of the clinically available antibiotics tested. Escherichia coli, Klebsiella, Serratia and Providencia were susceptible to LY 127935. Some resistant strains of Enterobacter, Proteus, Pseudomonas aeruginosa and Acinetobacter were also resistant to LY 127935, but many of the strains resistant to other antibiotics were susceptible to LY 127935. The activity of LY 127935 against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans and Streptococcus bovis was similar to that of cephalexin and cephradine. LY 127935 was not active against methicillin-resistant S. aureus nor enterococcus.

Aminoglycosides↗
PubMed1992

Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.

The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.

Drug Resistance, Microbial↗
PubMed1975

Methicillin-resistant staphylococci 1965-75.

Methicillin resistance in Staphylococcus aureus has been one of the major problems of gram positive infections in hospitals in the Zurich area. Up to 1971, about 20% of staphylococcal disease was caused by these peculiar organisms. Since 1972, however, a gradual decrease in the number of methicillin-resistant organisms has been observed, with an unprecedented low of 3% in 1975. The nearly 700 methicillin-resistant cultures that have isolated since 1965 exhibited, with rare exceptions, conventional group-II patterns of lysis in phage-typing and similar antibiotypes. It is suggested that all these isolates are derivatives of a strain which has long existed in the staphylococcal population. The reasons for the changes in the frequency of this strain as an agent causing staphylococcal disease are unclear. The use of penicillinase-resistant beta-lactam antibiotics in hospitals does not seem to play a major role in the distribution and spread or in the disappearance of this strain.

Bacteriophage Typing↗
PubMed1979

Australian evaluation of Autobac I with suggested interpretive and technical modifications.

Autobac I, a recently introduced semiautomated method for rapid antibiotic susceptibility testing, has been evaluated by comparison with the calibrated dichotomous sensitivity disk diffusion technique, which is routinely used in many Australian hospitals. Only the most common clinical isolates, Staphylococcus aureus, Escherichia coli, Klebsiella sp., and Proteus mirabilis, were included in this evaluation, and an overall interpretive agreement of 93% was obtained. However, an unusually high rate of discrepancy was noted in several organism-antibiotic combinations, in particular E. coli and P. mirabilis with ampicillin, S. aureus with penicillin, and methicillin-resistant S. aureus with methicillin, erythromycin, and clindamycin. The discrepancies associated with ampicillin have been reduced from 29 and 24% for E. coli and P. mirabilis, respectively, to less than 5% after the utilization of commercial 10-micrograms diffusion disks, in preference to the lower antibiotic content disks supplied by the Autobac manufacturer. Furthermore, modifications in the interpretive procedure have eliminated discrepancies associated with S. aureus and penicillin.

Ampicillin↗
PubMed1992

[Clinical studies on cefprozil granules in pediatric skin soft tissues infections].

Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

In vitro activity of the new glycopeptide decaplanin.

The activity of decaplanin, a new glycopeptide, was compared to that of vancomycin, teicoplanin and daptomycin. Decaplanin was two- to four-fold less active than vancomycin, telcoplanin and daptomycin against Staphylococcus aureus and Staphylococcus epidermidis, with an MIC90 of 2 micrograms/ml for methicillin-susceptible and 4 micrograms/ml for methicillin-resistant isolates. Decaplanin had activity similar to that of vancomycin against Streptococcus pyogenes, Streptococcus agalactiae, group C and G streptococci, with an MIC90 of 0.12 micrograms/ml. It was less active than the other agents against the viridans group streptococci (MIC90 4 micrograms/ml). The activity of decaplanin against enterococci (MIC90 4 micrograms/ml) was similar to that of vancomycin. Clostridium spp. were inhibited by 0.5 micrograms/ml, peptostreptococci and peptococci by 0.25 microgram/ml. Decaplanin was active from pH 5.5 to 7.5. Inoculum size had a minimal effect on MICs, and increased concentrations of Ca2+ and Mg2+ and 50% serum did not alter MICs or MBCs.

Anti-Bacterial Agents↗
PubMed2026

Genomic diversity and resistance determinants of staphylococci from cow and buffalo milk.

BACKGROUND: Staphylococci are important mastitis pathogens in dairy animals and serve as reservoirs of antimicrobial resistance genes (ARGs) having zoonotic potential. Genomic characterization of resistant isolates is essential to understand their diversity, resistance mechanisms, and One Health implications. METHODS AND RESULTS: A total of 363 cow and buffalo milk samples-including 108 from animals with mastitis-were screened, yielding 98 staphylococcal isolates, comprising 20 Staphylococcus aureus and 78 coagulase-negative staphylococci (CoNS). Antimicrobial susceptibility testing revealed resistance to cefoxitin (CoNS: 21.7%; S. aureus: 10%), tetracycline (CoNS: 19.2%; S. aureus: 10%), erythromycin (CoNS:16.7%; S. aureus: 10%), gentamicin (CoNS: 10.2%; S. aureus: 10%) and fluoroquinolone (CoNS: 10.2%), while the majority were sensitive to chloramphenicol, cotrimoxazole (~ 95%, each), linezolid (~ 97%), and vancomycin (100%). Nineteen isolates, including two S. aureus, were cefoxitin-resistant, and eight carried the mecA gene. Whole genome sequencing of these eight isolates revealed genome sizes ranging from 2.27 to 2.78 MB, with the methicillin resistant S. aureus (MRSA, ERSST98) isolate possessing the largest genome and the highest rRNA copy number. Comparative genomic analysis revealed various SCCmec types along with an extensive array of resistance determinants, encompassing aminoglycosides, macrolides, tetracyclines, efflux systems, and heavy metals, underscoring the multifaceted resistance repertoire of these strains. Virulence profiling of ERSST98 demonstrated a broad arsenal of adhesins, toxins, and biofilm‑associated genes, highlighting its pathogenic capacity. Mobile genetic elements with diverse plasmid replicons and insertion sequence families further contributed to genomic plasticity. CONCLUSIONS: Collectively, this study underscores the genomic diversity of methicillin-resistant staphylococci from dairy animals with extensive resistance determinants and highlights their zoonotic relevance within One Health framework.

Animals↗
PubMed2025

Co-existence of the oxazolidinone resistance genes cfr and optrA on a novel multiresistance plasmid from a methicillin-resistant Macrococcoides bohemicum strain.

OBJECTIVES: To identify and characterize the oxazolidinone resistance genes cfr and optrA from a methicillin-resistant Macrococcoides bohemicum strain of chicken origin. METHODS: The presence of mobile oxazolidinone resistance genes was detected by PCR. Antimicrobial susceptibility testing was conducted by broth microdilution. Transfer experiments were carried out to evaluate horizontal transferability of the plasmid. WGS was performed using a combination of Illumina NovaSeq/Oxford Nanopore PromethION platforms. RESULTS: The M. bohemicum strain HLJ23 exhibited an MDR phenotype and was positive for both cfr and optrA genes. WGS revealed that the genes cfr and optrA co-exist on the novel MDR plasmid pHLJ23-71kb. Although conjugation experiments were unsuccessful, plasmid pHLJ23-71kb could be transferred to Staphylococcus aureus RN4220 by electrotransformation. Genetic context analysis showed that the cfr and optrA together with another four antimicrobial resistance genes are located in an MDR region on plasmid pHLJ23-71kb. Sequence analysis suggested that this MDR region possibly originated from Mammaliicoccus or Staphylococcus spp. CONCLUSIONS: To the best of our knowledge, this study represents the first report of the oxazolidinone resistance genes cfr and optrA in the genus Macrococcoides. Furthermore, attention should be paid to the exchange of resistance determinants between members of the genera Staphylococcus, Mammaliicoccus and Macrococcoides.

Plasmids↗
PubMed2026

Antimicrobial-resistant Staphylococcus aureus isolated from Australian wildlife admitted to a veterinary hospital.

Although antimicrobial resistance (AMR) is a growing One Health concern, little is known about AMR in Staphylococcus aureus from Australian wildlife. This study investigated the occurrence, phenotypic AMR profiles, and genetic characteristics of S. aureus from six representative Australian wildlife species admitted to a wildlife hospital in Western Australia, including the western grey kangaroo (Macropus fuliginosus), quenda (Isoodon fusciventer), pelican (Pelecanus conspicillatus), galah (Eolophus roseicapilla), shingleback skink (Tiliqua rugosa) and long-necked turtle (Chelodina colliei). Staphylococcus aureus was isolated from 11.7% (21/180, 95% CI: 7.4%-17.3%) of the animals on admission. Whole genome sequencing identified 13 multi-locus sequence types (STs) and various virulence factors, including the human-specific immune evasion cluster (IEC). Resistance to at least one antimicrobial class was observed in 63.6% of the isolates. The blaZ, erm(T), aac(6')-aph(2″), and tet(L) AMR genes were detected in 63.6%, 13.6%, 4.5%, and 4.5% of S. aureus, respectively. After 7 days of hospitalisation, S. aureus was isolated from 16.5% (16/97, 95% CI: 9.7%-25.4%) of the animals, including two methicillin-resistant S. aureus (MRSA) isolated from two pelicans. The two MRSA were identified as community-associated MRSA clones (mecA-positive ST1-IV and ST93-IV), suggesting direct or indirect transmission between humans and wildlife during hospitalisation may have occurred. This study highlighted Australian wildlife may be a potential reservoir for genetically diverse antimicrobial-resistant S. aureus. AMR surveillance including wildlife using a One Health approach may be required.

Animals↗
PubMed1978

Use of a heavy inoculum in the in vitro evaluation of the anti-staphylococcal activity of 19 cephalosporins.

The in vitro activity of 19 cephalosporins against 105 clinical isolates of Staphylococcus aureus and S. epidermidis was determined by using a heavy inoculum, i.e., 10(8) to 10(9) organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against S. aureus, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible S. aureus than with the methicillin-susceptible S. epidermidis strains.

Bacteriological Techniques↗
PubMed1992

Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers.

Three separate single-dose studies were performed to define the disposition and pharmacokinetics of daptomycin in healthy volunteers. Daptomycin was administered as a single 14C-labeled dose (1.0 mg/kg of body weight) and as single doses between 0.5 and 6.0 mg/kg. All doses were intravenous. Antibacterial activity was determined from doses of 2.0, 3.0, 4.0, and 6.0 mg/kg against two strains of Staphylococcus aureus (one methicillin resistant) and one Enterococcus strain. After administration of 14C-labeled daptomycin, recovery of 14C in urine and feces accounted for 83% of the administered dose, with the greatest fraction (78%) appearing in the urine. Specific analysis for daptomycin in both urine and plasma indicated that metabolic products were present in urine, but total 14C in plasma consisted of daptomycin only. Doses between 0.5 and 6 mg/kg were linear, with a limited total body clearance (0.13 to 0.21 ml/min/kg) and a small volume of distribution (0.10 to 0.15 liter/kg). The small volume of distribution may be a factor of the high plasma protein binding (90 to 95%). Renal clearance made up 34 to 54% of total body clearance. Daptomycin demonstrated in vivo antibacterial activity against all three test strains, with the greatest activity observed against methicillin-resistant S. aureus. The predicted MIC for all three strains was approximately 13 micrograms/ml, corresponding to total (bound plus unbound) drug. On the basis of the drug's pharmacokinetics and antibacterial activity, doses of 4 to 6 mg/kg/day, possibly in divided doses, are predicted to be effective.

Adult↗
PubMed1992

In vitro activity of OPC-17116.

The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal to 0.25 microgram/ml. At less than or equal to 2 micrograms/ml, 90% of the Enterobacteriaceae were inhibited, which was comparable to or better than the activities of fleroxacin, ofloxacin, and lomefloxacin but less than the activity of ciprofloxacin. OPC-17116 inhibited 90% of the staphylococci tested at less than or equal to 0.25 micrograms/ml, but it did not inhibit methicillin-resistant, ciprofloxacin-resistant Staphylococcus aureus or Staphylococcus epidermidis. Group A, B, C, F, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.5 microgram/ml, being four-fold more active than ciprofloxacin and ofloxacin. Tosufloxacin was the most active agent tested against gram-positive cocci. OPC-17116 inhibited Bacteroides fragilis at 4 micrograms/ml. There was a minimal effect of inoculum size on MIC, and the MBCs were within 1 dilution of the MICs. The activity of OPC-17116 was decreased at pH 6 and in the presence of high Mg2+ concentrations, but it was unaffected by human serum. OPC-17116 showed a postantibiotic effect against Pseudomonas aeruginosa and Staphylococcus aureus similar to the postantibiotic effects reported for other fluoroquinolones. The frequency of spontaneous single-step resistance was low (less than 10(-9)), but repeated passage of organisms in the presence of OPC-17116 resulted in the selection of resistant isolates.

Anti-Infective Agents↗
PubMed1992

Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates.

DU-6859, (-)-7-[(7S)-amino-5-azaspiro(2,4)heptan-5-yl]-8-chloro-6- fluoro-1-[(1R,2R)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinol one-3- carboxylic acid, is a new fluoroquinolone with antibacterial activity which is significantly better than those of currently available quinolones. The MICs for 90% of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates (MIC90s) were 0.1, 3.13, 0.1, and 0.39 microgram/ml, respectively. MIC50s of DU-6859 against quinolone-resistant, methicillin-resistant S. aureus were 8-, 32-, 64-, and 128-fold lower than those of tosufloxacin and sparfloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin, respectively. DU-6859 inhibited the growth of all strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.1 and 0.2 microgram/ml, respectively, and was more active against enterococci than the other quinolones tested. Although the activity of DU-6859 against Pseudomonas aeruginosa was roughly comparable to that of ciprofloxacin at the MIC50 level, it was fourfold more active than ciprofloxacin at the MIC90 level. DU-6859 was also more active against other glucose-nonfermenting bacteria, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, than the other drugs tested. Strains of Bacteroides fragilis and Peptostreptococcus spp. were susceptible to DU-6859; MIC90s were 0.39 and 0.2 microgram/ml, respectively. DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae. The action of DU-6859 against the clinical isolates was bactericidal at concentrations near the MICs. DU-6859 activity was not affected by different media, pH, inoculum size, or human serum but was decreased in human urine.

Anti-Infective Agents↗
PubMed1978

Chromosomal map location of the methicillin resistance determinant in Staphylococcus aureus.

Three-factor genetic crosses performed by transformation have shown that the methicillin resistance determinant of Staphylococcus aureus strain DU4916 (the mec-4916 marker) is linked to a novobiocin resistance (Novr) marker (nov-142) and mutational sites affecting pyrimidine (pyr-141), purine (pur-102), and histidine (hisG15) biosynthesis in S. aureus strain 8325. The linkage group thus defined is pyr-141-hisG15-nov-142-pur-102-mec-4916. Phage 80alpha previously propagated on a novobiocin-resistant, methicillin-sensitive (Mecs) 8325 strain was used to infect 21 novobiocin-sensitive, methicillin-resistant clinical isolates (including strain DU4916). Among the novobiocin-resistant transductants so obtained from each recipient, between 1 and 5% were methicillin sensitive (reflecting cotransduction of Novr and Mecs). These results are consistent with the genetic determinant of methicillin resistance having a single chromosomal locus in most, if not all, strains of S. aureus.

Chromosome Mapping↗
PubMed1992

Isolation and characterization of a Tn551-autolysis mutant of Staphylococcus aureus.

A Lyt- mutant with reduced autolytic activity was isolated after Tn551 mutagenesis of the methicillin-susceptible Staphylococcus aureus laboratory strain RN450. The Lyt- phenotype could be transferred back into the parent and into a variety of other S. aureus strains by transduction of the transposon marker. Southern analysis has located the Tn551 insert to a 3.2-kb HindIII DNA fragment on the SmaI B fragment of the staphylococcal chromosome. The Lyt- phenotype included reduced rates of cell wall turnover and autolysis induced by detergent or methicillin treatment; however, the rate of methicillin-induced killing was not affected. Peptidoglycans prepared from the parental and mutant cells showed identical muropeptide compositions, as resolved by a high-resolution high-pressure liquid chromatography technique. On the other hand, LiCl extracts of the mutant cells contained reduced amounts of total protein and lower specific cell wall-degrading activity compared with those of extracts of parental cells. The profile of bacteriolytic enzymes as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed multiple band differences between mutant and parental cells; a major lytic band with properties characteristic of the staphylococcal endo-beta-N-acetylglucosaminidase was completely absent from the Lyt- cells. The Lyt- phenotype transduced into a series of methicillin-resistant strains of both homogeneous and heterogeneous phenotypes caused only a modest decrease in the level of methicillin resistance, as determined by population analysis.

Bacteriolysis↗
PubMed2026

Genomic and virulence characteristics of Staphylococcus aureus isolates from foodborne outbreak cases.

This study aimed to investigate the genomic characteristics, enterotoxin production, and antimicrobial resistance profiles of Staphylococcus aureus isolates associated with foodborne outbreaks. A total of 19 bacterial isolates were collected from foodborne outbreaks in Guizhou Province, China between 2014 and 2023. Following biochemical identification, all isolates were confirmed as S. aureus. Phylogenetic analysis divided the 19 strains into seven branches. Enterotoxin production was detected using standard microbiological techniques and immunoassays. Antimicrobial susceptibility was evaluated using the broth microdilution method. Whole-genome sequencing and subsequent bioinformatic analyses were conducted to characterize virulence genes, antimicrobial resistance genes, multilocus sequence typing (MLST) genotypes, and phylogenetic relationships among the isolates. This study found that all strains produced classical staphylococcal enterotoxins, with staphylococcal enterotoxin (SEA) showing the highest detection rate (63.16%). Virulence gene profiling revealed widespread presence of hlb, hlgA, nuc, clfB, spa, and set genes. All strains were resistant to penicillin, with high resistance rates for erythromycin and cefoxitin. Multidrug resistance occurred in 11 of the 19 strains, and 22 resistance genes were identified. MLST analysis showed that ST6 and ST59 were the dominant types, with ST59 methicillin-resistant S. aureus (MRSA) strains displaying stronger resistance and more virulence determinants. These findings provide insights into the virulence, resistance, and molecular epidemiology of S. aureus strains involved in foodborne outbreaks, and may provide useful information for future surveillance and risk assessment.

Staphylococcus aureus↗
PubMed2023

Teicoplanin associated gene tcaA inactivation increases persister cell formation in Staphylococcus aureus.

Staphylococcus aureus is part of normal human flora and is widely associated with hospital-acquired bacteremia. S. aureus has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant S. aureus (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. S. aureus has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the S. aureus glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in S. aureus persister cells formation, and ΔtcaA dependent persisters' ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of glyS and sgtB. The RNA-seq data revealed a significant decrease in tcaA (p = 0.008) and tcaB (p = 0.04) expression while tcaR was not significantly altered. We knocked down tcaA, tcaB, and tcaR using CRISPR-dCas9 and the results showed that when tcaA was suppressed by dCas9, a significant increase was witnessed in persister cells while tcaB suppression did not induce persistence. The results were further evaluated by creating a tcaA mutant that showed ΔtcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that tcaA is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in S. aureus.

MRSA↗