scholarly journals Progression of β-Lactam Resistance in Staphylococcus aureus

2021 ◽  
Author(s):  
Antresh Kumar ◽  
Manisha Kaushal
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Proteins ◽  
Efflux Pump ◽  
Human Pathogen ◽  
Topical Antibiotics ◽  
Invasive Infections ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Mrsa Strains ◽  
Second Wave

Staphylococcus aureus is a notorious human pathogen that causes superficial and invasive infections both in nosocomial and community-acquired settings. The prevalence of staphylococcal infections became more challenging after emerging resistance against topical antibiotics. S. aureus evolved resistance to β-lactam antibiotics due to modification and expression of penicillin-binding proteins (PBP), inactivation of drug by β-lactamase synthesis, limiting uptake of drug by biofilm formation, and reducing uptake by expression of efflux pump. The wave of resistance was first observed in penicillin by β-lactamase production and PBPs modification. The second wave of resistance emerged to methicillin by appearing methicillin-resistant S. aureus (MRSA) strains. Cephalosporin has long been used as the last resort for preventing MRSA infections, but resistant strains appeared during treatment. In progression to control MRSA or related infections, carbapenems have been used but strains developed resistance. S. aureus is among the high-priority resistance organisms that need renewed efforts for the research and development of new antibiotics and innovative preventive approaches. However, a lot of toiling is involved in devising an effective treatment against drug resistant S. aureus. This chapter aim is to retrospectively determine the progression of resistance in S. aureus, against different β-lactam antibiotics and their challenges of medication.

scholarly journals FmhA and FmhC of Staphylococcus aureus incorporate serine residues into peptidoglycan cross-bridges

2020 ◽  
Vol 295 (39) ◽  
pp. 13664-13676 ◽  
Author(s):  
Stephanie Willing ◽  
Emma Dyer ◽  
Olaf Schneewind ◽  
Dominique Missiakas
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Binding Proteins ◽  
Penicillin Binding Proteins ◽  
Daughter Cells ◽  
Cross Bridge ◽  
Resistant Strains ◽  
The Cross ◽  
Cross Bridges ◽  
Adjacent Wall

Staphylococcal peptidoglycan is characterized by pentaglycine cross-bridges that are cross-linked between adjacent wall peptides by penicillin-binding proteins to confer robustness and flexibility. In Staphylococcus aureus, pentaglycine cross-bridges are synthesized by three proteins: FemX adds the first glycine, and the homodimers FemA and FemB sequentially add two Gly-Gly dipeptides. Occasionally, serine residues are also incorporated into the cross-bridges by enzymes that have heretofore not been identified. Here, we show that the FemA/FemB homologues FmhA and FmhC pair with FemA and FemB to incorporate Gly-Ser dipeptides into cross-bridges and to confer resistance to lysostaphin, a secreted bacteriocin that cleaves the pentaglycine cross-bridge. FmhA incorporates serine residues at positions 3 and 5 of the cross-bridge. In contrast, FmhC incorporates a single serine at position 5. Serine incorporation also lowers resistance toward oxacillin, an antibiotic that targets penicillin-binding proteins, in both methicillin-sensitive and methicillin-resistant strains of S. aureus. FmhC is encoded by a gene immediately adjacent to lytN, which specifies a hydrolase that cleaves the bond between the fifth glycine of cross-bridges and the alanine of the adjacent stem peptide. In this manner, LytN facilitates the separation of daughter cells. Cell wall damage induced upon lytN overexpression can be alleviated by overexpression of fmhC. Together, these observations suggest that FmhA and FmhC generate peptidoglycan cross-bridges with unique serine patterns that provide protection from endogenous murein hydrolases governing cell division and from bacteriocins produced by microbial competitors.

scholarly journals Antibiotic Resistance and Virulence Gene Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated from Healthy Edible Marine Fish

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Justine Fri ◽  
Henry A. Njom ◽  
Collins N. Ateba ◽  
Roland N. Ndip
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Marine Fish ◽  
Control Strategies ◽  
Virulence Gene ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Vancomycin Mics ◽  
Resistant Strains ◽  
Mrsa Strains

Thirty-three (33) isolates of methicillin-resistant Staphylococcus aureus (MRSA) from healthy edible marine fish harvested from two aquaculture settings and the Kariega estuary, South Africa, were characterised in this study. The phenotypic antimicrobial susceptibility profiles to 13 antibiotics were determined, and their antibiotic resistance determinants were assessed. A multiplex PCR was used to determine the epidemiological groups based on the type of SCCmec carriage followed by the detection of staphylococcal enterotoxin-encoding genes sea-sed and the Panton Valentine leucocidin gene (pvl). A high antibiotic resistance percentage (67–81%) was observed for Erythromycin, Ampicillin, Rifampicin, and Clindamycin, while maximum susceptibility to Chloramphenicol (100%), Imipenem (100%), and Ciprofloxacin (94%) was recorded. Nineteen (58%) of the MRSA strains had Vancomycin MICs of ≤2 μg/mL, 4 (12%) with MICs ranging from 4–8 μg/mL, and 10 (30%) with values ≥16 μg/mL. Overall, 27 (82%) isolates were multidrug-resistant (MDR) with Erythromycin-Ampicillin-Rifampicin-Clindamycin (E-AMP-RIP-CD) found to be the dominant antibiotic-resistance phenotype observed in 4 isolates. Resistance genes such as tetM, tetA, ermB, blaZ, and femA were detected in two or more resistant strains. A total of 19 (58%) MRSA strains possessed SCCmec types I, II, or III elements, characteristic of healthcare-associated MRSA (HA-MRSA), while 10 (30%) isolates displayed SCCmec type IVc, characteristic of community-associated MRSA (CA-MRSA). Six (18%) of the multidrug-resistant strains of MRSA were enterotoxigenic, harbouring the see, sea, or sec genes. A prevalence of 18% (6/33) was also recorded for the luk-PVL gene. The findings of this study showed that marine fish contained MDR-MRSA strains that harbour SCCmec types, characteristic of either HA-MRSA or CA-MRSA, but with a low prevalence of enterotoxin and pvl genes. Thus, there is a need for continuous monitoring and implementation of better control strategies within the food chain to minimise contamination of fish with MDR-MRSA and the ultimate spread of the bug.

scholarly journals Multiply- and methicillin-resistantStaphylococcus aureusstrains isolated in the German Democratic Republic in 1985 and 1986

1987 ◽  
Vol 99 (3) ◽  
pp. 603-612 ◽  
Author(s):  
W. Witte ◽  
Chr. Braulke
Keyword(s):  
Staphylococcus Aureus ◽  
Nosocomial Infection ◽  
Democratic Republic ◽  
Phage Typing ◽  
Biochemical Traits ◽  
Strain Differentiation ◽  
Resistance Determinants ◽  
Basic Set ◽  
Resistant Strains ◽  
Mrsa Strains

SUMMARYMultiply- and methicillin-resistantStaphylococcus aureus(MRSA) strains have been isolated from five small outbreaks of nosocomial infection in five different hospitals. The MRSA were typed by phage patterns, biochemical traits, resistance phenotypes and plasmid patterns. Three different groups of strains can be distinguished. The MRSA from three outbreaks in one country share identical characters.Phage typing by the use of the International Basic Set for Phage Typing staphylococci as well as experimental phages does not completely discriminate between the strains. Attribution of several resistance determinants to plasmids in two of the described strain groups proved valuable for strain differentiation.These multiply-resistant strains are sensitive to vancomycin and to rifampicin.

scholarly journals 554. The Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus Causing Bacteremia in Hiroshima, Japan During 2008–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S263-S263
Author(s):  
Hiroki Kitagawa ◽  
Junzo Hisatsune ◽  
Hiroki Ohge ◽  
Motoyuki Sugai
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sccmec Type ◽  
University Hospital ◽  
Methicillin Resistant ◽  
Type Iv ◽  
Time Period ◽  
Invasive Infections ◽  
Toxic Shock Syndrome Toxin ◽  
Mrsa Strains

Abstract Background Recently, the Japanese intrinsic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone (CA-MRSA/J), classified as sequence type (ST) 8 carrying staphylococcal cassette chromosome mec (SCCmec) type IVl (ST8-IVl), has been identified that causes invasive infections similar to those of USA300 clone. However, epidemiological information regarding epidemic CA-MRSA clones is limited in Japan. This study was performed to investigate the changing epidemiology of MRSA causing bacteremia in Japan. Methods We performed whole-genome sequencing of MRSA isolates causing bacteremia at Hiroshima University Hospital between January 2008 and December 2017. MRSA isolates were subjected to multilocus sequence typing, SCCmec typing and were analyzed for virulence factors. Clinical data of patients with MRSA bacteremia were analyzed. Results A total of 193 MRSA strains causing bacteremia were identified during the study period. Among these, most belonged to ST764-IIa (30%; 59 of 193) and ST5-IIa (26.9%; 52 of 193). The proportion of ST5-IIa MRSA decreased from 39.6% (42 of 106) in 2008–2012 to 11.5% (10 of 87) in 2013–2017, and that of ST764-IIa MRSA increased from 23.6% (25 of 106) to 39.1% (34 of 87) in the same time period. The proportion of CA-MRSA (MRSA carrying SCCmec type IV or V) increased from 28.3% (30 of 106) in 2008–2012 to 42.5% (37 of 87) in 2013–2017. In CA-MRSA strains, clonal complex (CC) 8-IV MRSA was predominant (76.1%; 51 of 67). Those belonging to CC8-IV MRSA isolates were ST380-IVc (18 of 51), ST8-IVl (CA-MRSA/J; 15 of 51), ST8-IVj (15 of 51), ST8-IVa (2 of 51), and ST4803-IVl (1 of 51). The rate of hospital-onset infections of ST380-IVc, ST8-IVl, and ST8-IVj were 83.3%, 46.7%, and 60%, respectively. In CA-MRSA/J strains, including their variants (e.g., ST4803-IVl), 14 of 16 strains (87.5%) carried genes for toxic shock syndrome toxin (tst-1), enterotoxin C (sec), and enterotoxin L (sel), while none of the ST380-IVc and ST8-IVj MRSA strains carried these genes. Conclusion During the study period of 10 years, predominant ST5-IIa MRSA causing hospital-onset infections was replaced by ST764-IIa MRSA. In CA-MRSA clone, ST380-IVc, ST8-IVl (CA-MRSA/J), and ST8-IVj were dominant and have already spread to the healthcare environment. Disclosures All authors: No reported disclosures.

scholarly journals Missense Mutations in PBP2A Affecting Ceftaroline Susceptibility Detected in Epidemic Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Clonotypes ST228 and ST247 in Western Switzerland Archived since 1998

2015 ◽  
Vol 59 (4) ◽  
pp. 1922-1930 ◽  
Author(s):  
William L. Kelley ◽  
Ambre Jousselin ◽  
Christine Barras ◽  
Emmanuelle Lelong ◽  
Adriana Renzoni
Keyword(s):  
Staphylococcus Aureus ◽  
University Hospital ◽  
Surveillance Program ◽  
Missense Mutations ◽  
Unknown Parameters ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Mrsa Strains

ABSTRACTThe development and maintenance of an arsenal of antibiotics is a major health care challenge. Ceftaroline is a new cephalosporin with activity against methicillin-resistantStaphylococcus aureus(MRSA); however, no reports concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We tested thein vitroactivity of ceftaroline against an archived set of 60 MRSA strains from the University Hospital of Geneva collected from 1994 to 2003. Our results surprisingly revealed ceftaroline-resistant strains (MIC, >1 μg/ml in 40/60 strains; EUCAST breakpoints, susceptible [S], ≤1 μg/ml; resistant [R], >1 μg/ml) were present from 1998 to 2003. The detected resistant strains predominantly belonged to sequence type 228 (ST228) (South German clonotype) but also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations (primarily E239K) recently described for MRSA strains collected in Thailand and Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance program. We also found that similar allosteric domain PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent external ST228 MRSA set obtained from the nearby University Hospital of Lausanne, Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance was observed in our archived strains (including two examples of an MIC of 4 µg/ml for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at least as far back as 1998, considerably predating the commercial introduction of ceftaroline. Our results reinforce the notion that unknown parameters can potentially exert selective pressure on PBP2A that can subsequently modulate ceftaroline resistance.

scholarly journals Modulation ofccrABExpression and SCCmecExcision by an Inverted Repeat Element and SarS in Methicillin-Resistant Staphylococcus aureus

2015 ◽  
Vol 59 (10) ◽  
pp. 6223-6232 ◽  
Author(s):  
Shijie Zhang ◽  
Ronghua Ma ◽  
Xiaoyu Liu ◽  
Xu Zhang ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Inverted Repeat ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Regulatory Mechanism ◽  
Human Pathogen ◽  
Entire Family ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Dna Affinity Chromatography

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) is a notorious human pathogen that can cause a broad spectrum of infections. MRSA strains are resistant to almost the entire family of β-lactam antibiotics due to the acquisition of staphylococcal cassette chromosomemec(SCCmec). The chromosome cassette recombinases A and B, encoded byccrABgenes located on SCCmec, play a key role in the excision of SCCmec. Studies have shown thatccrABgenes are expressed in only a minority of cells, suggesting the involvement of a subtle regulatory mechanism inccrABexpression which has not been uncovered. Here, we found that an inverted repeat (IR) element, existing extensively and conservatively within theccrABpromoter of different SCCmectypes, played a repressive role inccrABexpression and SCCmecexcision in MRSA strain N315. Replacement of the IR sequence led to a significant increase inccrABexpression and curing of SCCmecfrom strain N315 cells. In addition, we identified the transcriptional regulator SarS using DNA-affinity chromatography and further demonstrated that SarS can bind to the IR sequence and upregulateccrABexpression and SCCmecexcision. These findings reveal a molecular mechanism regulatingccrABexpression and SCCmecexcision and may provide mechanic insights into the lateral transfer of SCCmecand spread of antibiotic resistance inS. aureus.

scholarly journals Discovery of Brominated Alboflavusins With Anti-MRSA Activities

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Li ◽  
Wuyundalai Bao ◽  
Haoyue Zhang ◽  
Zhitang Lyu ◽  
Yihua Chen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Type Strain ◽  
Wild Type Strain ◽  
Production Medium ◽  
Wild Type ◽  
Methicillin Resistant ◽  
New Antibiotics ◽  
Mrsa Strains ◽  
New Compounds

As methicillin-resistant Staphylococcus aureus (MRSA) is becoming a serious pathogenic threaten to human health worldwide, there is an urgent need to discover new antibiotics for the treatment of MRSA infections. Alboflavusins (AFNs) are a group of halogenated cyclohexapeptides with anti-MRSA activities. In this study, two novel brominated AFN congeners (compounds 1 and 2) were isolated from the wild-type strain Streptomyces alboflavus sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds 3 and 5) and a known (compound 4) dehelogenated AFN congeners were isolated from S. alboflavus ΔafnX, in which the tryptophan halogenase gene afnX was inactivated. The structures of these compounds were assigned by careful NMR and MS analyses. The anti-MRSA activities of varied AFN congeners were assessed against different MRSA strains, which revealed that compounds 1 and 2 with bromine displayed effective activities against the tested MRSA strains. Especially, compound 2 showed good anti-MRSA activity, while compounds 3, 4, and 5 without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.

scholarly journals Phenotypic and Molecular Typing of Nosocomial Methicillin-Resistant Staphylococcus aureus Strains Susceptible to Gentamicin Isolated in France from 1995 to 1997

2000 ◽  
Vol 38 (1) ◽  
pp. 185-190
Author(s):  
Jacques-Olivier Galdbart ◽  
Anne Morvan ◽  
Nevine El Solh
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Typing ◽  
Insertion Sequence ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Phage Typing ◽  
Methicillin Resistant ◽  
Before And After ◽  
Resistant Strains ◽  
Mrsa Strains

ABSTRACT Methicillin-resistant strains susceptible to gentamicin (Gm s MRSA) have emerged since 1993 in several French hospitals. To study whether particular clones have spread in various French cities and whether some clones are related to gentamicin-resistant (Gm r ) MRSA strains, various methods (antibiotyping, phage typing, determination of Sma I macrorestriction patterns before and after hybridization with IS 256 transposase and aacA-aphD probes) were used to compare 62 Gm s MRSA strains isolated from 1995 to 1997 in nine cities and 15 Gm r MRSA strains. Eighteen major Sma I genotypes were identified, of which 11 included only Gm s MRSA strains and 5 included only Gm r MRSA strains. Each of the Gm r MRSA strains contained 6 to 13 Sma I fragments hybridizing with the insertion sequence IS 256 , of which a single band also hybridized with the aacA-aphD gene. No such hybridizing sequences were detected in 60 of the 62 Gm s MRSA strains. Thus, the divergence between Gm r and Gm s MRSA strains is revealed, not only by their distributions in distinct Sma I genotypes but also by the differences in hybridization patterns. Two of the 62 Gm s MRSA strains had the uncommon feature of carrying several Sma I bands hybridizing with IS 256 , suggesting that they are possibly related to the Gm r MRSA strains grouped in the same Sma I genotype. Five of the 11 Sma I genotypes including only Gm s MRSA strains contained strains from diverse cities, isolated during different years and with different antibiograms, suggesting that some clones have spread beyond their cities of origin and persisted.

scholarly journals Inhibition of biofilm produced by methicillin-resistant Staphylococcus aureus (MRSA) by thymoquinone.

2021 ◽  
Vol 3 (3) ◽  
pp. 65-68
Author(s):  
Muhammad Sohail ◽  
Zakia Latif ◽  
Abid Hussain ◽  
Hafiz Ghulm Murtaza
Keyword(s):  
Public Health ◽  
Staphylococcus Aureus ◽  
Essential Oil ◽  
Nigella Sativa ◽  
Health Concern ◽  
Antibiofilm Activity ◽  
Mortality And Morbidity ◽  
New Antibiotics ◽  
Financial Concern ◽  
Mrsa Strains

Multidrug resistance is a leading public health challenge that is causing a significant increase in mortality and morbidity. If antimicrobial resistance (AMR) remains unsolved, it may cause 10 million deaths every year. Along with a public health concern, it is also a financial concern that would cause 2-3.5% reduction in Gross Domestic Product (GDP) and a 100 trillion USD loss to the world. One of the ways to combat AMR is to discover new antibiotics.  This study was aimed to evaluate the antibiofilm and antibacterial potencies of essential oil of Nigella sativa. Standard microbiological guidelines (CLSI) were used for the identification and antibiogram of selected strains of MRSA. Moreover, a time-kill assay of MRSA against Thymoquinone extracted from Nigella Sativa was also performed. Five strains, including four MRSA strains from implants related infections and one standard strain ATCC 25923, were examined. GC-MS identified components of essential oil of Nigella Sativa. Thymoquinone and p-cymene, major compounds of essential oil, were subjected to antibacterial and antibiofilm activities. Thymoquinone revealed strong inhibitory activities against MRSA strains. Zone inhibition measured 22 to 44 mm, and MIC values ranged from 26 to 43 Ul/mL. Thymoquinone also exhibited strong antibiofilm activity against biofilm producer MDR strains of Staphylococcus aureus.

Sign in / Sign up

Export Citation Format

Share Document