DNA Repair in Staphylococcus aureus

2021 ◽  
Author(s):  
Kam Pou Ha ◽  
Andrew M. Edwards
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Repair ◽  
Antibiotic Therapy ◽  
Host Response ◽  
Common Cause ◽  
Content Type ◽  
Host Environment ◽  
Staphylococcal Infections ◽  
Invasive Infections

Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequently become chronic or recurrent, demonstrating a remarkable ability of S. aureus to withstand the hostile host environment.

scholarly journals Iron-Mediated Control of Pseudomonas aeruginosa-Staphylococcus aureus Interactions in the Cystic Fibrosis Lung

2015 ◽  
Vol 197 (14) ◽  
pp. 2250-2251 ◽  
Author(s):  
Patricia M. Barnabie ◽  
Marvin Whiteley
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Patient Outcomes ◽  
Cystic Fibrosis Lung ◽  
Bacterial Survival ◽  
Content Type ◽  
Host Environment ◽  
Bacterial Interactions

Communication is an important factor for bacterial survival, growth, and persistence. Much work has examined both inter- and intraspecies interactions and their effects on virulence. Now, researchers have begun to explore the ways in which host-modulated factors can impact bacterial interactions and subsequently affect patient outcomes. In this issue, two papers discuss how the host environment alters interactions between the pathogensPseudomonas aeruginosaandStaphylococcus aureus, largely in the context of cystic fibrosis.

scholarly journals Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

2020 ◽  
Vol 65 (1) ◽  
pp. e01746-20 ◽  
Author(s):  
Itaru Nakamura ◽  
Tetsuo Yamaguchi ◽  
Kotaro Aoki ◽  
Yuri Miura ◽  
Satoko Sato ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Antibiotic Therapy ◽  
Combination Treatment ◽  
Psoas Abscess ◽  
Synergistic Effects ◽  
Vertebral Osteomyelitis ◽  
Gene Sequencing ◽  
Content Type ◽  
Synergy Test

ABSTRACTWe applied combination antibiotic therapy to treat vertebral osteomyelitis and a psoas abscess caused by glycopeptide-intermediate (MIC, 2 μg/ml) and daptomycin-nonsusceptible (>2 μg/ml) methicillin-resistant Staphylococcus aureus. The Etest synergy test showed the largest synergistic effects for imipenem/cilastatin and fosfomycin. Whole-gene sequencing showed amino acid changes in SA0802, SA1193 (mprF), and SA1531 (ald). Four weeks of combination treatment using imipenem/cilastatin (1.5 g per day) and fosfomycin (4.0 g per day) resulted in clinical improvement.

scholarly journals Absence of Patient-to-Patient Intrahospital Transmission of Staphylococcus aureus as Determined by Whole-Genome Sequencing

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
S. Wesley Long ◽  
Stephen B. Beres ◽  
Randall J. Olsen ◽  
James M. Musser
Keyword(s):  
Public Health ◽  
Staphylococcus Aureus ◽  
Hospital Setting ◽  
Nosocomial Transmission ◽  
Hospital System ◽  
Content Type ◽  
Hospital Infection Control ◽  
Invasive Infections ◽  
Sterile Site ◽  
Transmission Studies

ABSTRACT Nosocomial transmission of pathogens is a major health care challenge. The increasing spread of antibiotic-resistant strains represents an ongoing threat to public health. Previous Staphylococcus aureus transmission studies have focused on transmission of S. aureus between asymptomatic carriers or used low-resolution typing methods such as multilocus sequence typing (MLST) or spa typing. To identify patient-to-patient intrahospital transmission using high-resolution genetic analysis, we sequenced the genomes of a consecutive set of 398 S. aureus isolates from sterile-site infections. The S. aureus strains were collected from four hospitals in the Houston Methodist Hospital System over a 6-month period. Importantly, we discovered no evidence of transmission of S. aureus between patients with sterile-site infections. The lack of intrahospital transmission may reflect a fundamental difference between day-to-day transmission events in the hospital setting and the more frequently studied outbreak scenarios. IMPORTANCE Previous studies have suggested that nosocomial transmission of S. aureus is common. Our data revealed an unexpected lack of evidence for intrahospital transmission of S. aureus between patients with invasive infections. This finding has important implications for hospital infection control and public health efforts. In addition, our data demonstrate that highly related pools of S. aureus strains exist in the community which may complicate outbreak investigations.

scholarly journals Effect of Antimicrobial and Physical Treatments on Growth of Multispecies Staphylococcal Biofilms

2017 ◽  
Vol 83 (12) ◽  
Author(s):  
Elizabeth J. Stewart ◽  
David E. Payne ◽  
Tianhui Maria Ma ◽  
J. Scott VanEpps ◽  
Blaise R. Boles ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Orthopedic Implants ◽  
Response To Treatment ◽  
Content Type ◽  
High Ph ◽  
Staphylococcal Infections ◽  
Physical Treatments ◽  
Antimicrobial Treatments ◽  
Multispecies Biofilms

ABSTRACT The prevalence and structure of Staphylococcus aureus and Staphylococcus epidermidis within multispecies biofilms were found to depend sensitively on physical environment and antibiotic dosage. Although these species commonly infect similar sites, such as orthopedic implants, little is known about their behavior in multispecies communities, particularly in response to treatment. This research establishes that S. aureus is much more prevalent than S. epidermidis when simultaneously seeded and grown under unstressed conditions (pH 7, 37°C) in both laboratory and clinical strains. In multispecies communities, S. epidermidis is capable of growing a more confluent biofilm when the addition of S. aureus is delayed 4 to 6 h during 18 h of growth. Different vancomycin dosages generate various behaviors: S. epidermidis is more prevalent at a dose of 1.0 μg/ml vancomycin, but reduced growth of both species occurs at 1.9 μg/ml vancomycin. This variability is consistent with the different MICs of S. aureus and S. epidermidis. Growth at higher temperature (45°C) results in an environment where S. aureus forms porous biofilms. This porosity allows S. epidermidis to colonize more of the surface, resulting in detectable S. epidermidis biomass. Variations in pH result in increased prevalence of S. epidermidis at low pH (pH 5 and 6), while S. aureus remains dominant at high pH (pH 8 and 9). This work establishes the structural variability of multispecies staphylococcal biofilms as they undergo physical and antimicrobial treatments. It provides a basis for understanding the structure of these communities at infection sites and how treatments disrupt their multispecies behaviors. IMPORTANCE Staphylococcus aureus and Staphylococcus epidermidis are two species of bacteria that are commonly responsible for biofilm infections on medical devices. Biofilms are structured communities of bacteria surrounded by polysaccharides, proteins, and DNA; bacteria are more resistant to antimicrobials as part of a biofilm than as individual cells. This work investigates the structure and prevalence of these two organisms when grown together in multispecies biofilms and shows shifts in the behavior of the polymicrobial community when grown in various concentrations of vancomycin (an antibiotic commonly used to treat staphylococcal infections), in a high-temperature environment (a condition previously shown to lead to cell disruption and death), and at low and high pH (a change that has been previously shown to soften the mechanical properties of staphylococcal biofilms). These shifts in community structure demonstrate the effect such treatments may have on multispecies staphylococcal infections.

scholarly journals Staphylococcus aureus Responds to Physiologically Relevant Temperature Changes by Altering Its Global Transcript and Protein Profile

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Raeven A. Bastock ◽  
Emily C. Marino ◽  
Richard E. Wiemels ◽  
Donald L. Holzschu ◽  
Rebecca A. Keogh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Environmental Conditions ◽  
Large Temperature ◽  
Small Scale ◽  
Content Type ◽  
Temperature Changes ◽  
Invasive Infections ◽  
The Impact ◽  
Definite Temperature

ABSTRACT Staphylococcus aureus is an opportunistic pathogen that colonizes the anterior nares of 30 to 50% of the population. Colonization is most often asymptomatic; however, self-inoculation can give rise to potentially fatal infections of the deeper tissues and blood. Like all bacteria, S. aureus can sense and respond to environmental cues and modify gene expression to adapt to specific environmental conditions. The transition of S. aureus from the nares to the deeper tissues and blood is accompanied by changes in environmental conditions, such as nutrient availability, pH, and temperature. In this study, we perform transcriptomics and proteomics on S. aureus cultures growing at three physiologically relevant temperatures, 34°C (nares), 37°C (body), and 40°C (pyrexia), to determine if small scale, biologically meaningful alterations in temperature impact S. aureus gene expression. Results show that small but definite temperature changes elicit a large-scale restructuring of the S. aureus transcriptome and proteome in a manner that, most often, inversely correlates with increasing temperature. We also provide evidence that a large majority of these changes are modulated at the posttranscriptional level, possibly by sRNA regulatory elements. Phenotypic analyses were also performed to demonstrate that these changes have physiological relevance. Finally, we investigate the impact of temperature-dependent alterations in gene expression on S. aureus pathogenesis and demonstrate decreased intracellular invasion of S. aureus grown at 34°C. Collectively, our results demonstrate that small but biologically meaningful alterations in temperature influence S. aureus gene expression, a process that is likely a major contributor to the transition from a commensal to pathogen. IMPORTANCE Enteric bacterial pathogens, like Escherichia coli, are known to experience large temperature differences as they are transmitted through the fecal oral route. This change in temperature has been demonstrated to influence bacterial gene expression and facilitate infection. Staphylococcus aureus is a human-associated pathogen that can live as a commensal on the skin and nares or cause invasive infections of the deeper tissues and blood. Factors influencing S. aureus nasal colonization are not fully understood; however, individuals colonized with S. aureus are at increased risk of invasive infections through self-inoculation. The transition of S. aureus from the nose (colonization) to the body (infection) is accompanied by a modest but definite temperature increase, from 34°C to 37°C. In this study, we investigate whether these host-associated small temperature changes can influence S. aureus gene expression. Results show widespread changes in the bacterial transcriptome and proteome at three physiologically relevant temperatures (34°C, 37°C, and 40°C).

scholarly journals Novel Synthetic (Poly)Glycerolphosphate-Based Antistaphylococcal Conjugate Vaccine

2013 ◽  
Vol 81 (7) ◽  
pp. 2554-2561 ◽  
Author(s):  
Quanyi Chen ◽  
Jay Dintaman ◽  
Andrew Lees ◽  
Goutam Sen ◽  
David Schwartz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Conjugate Vaccine ◽  
Animal Studies ◽  
Lipoteichoic Acid ◽  
Gram Positive ◽  
Content Type ◽  
Cpg Oligodeoxynucleotides ◽  
Staphylococcal Infections

ABSTRACTStaphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intactStaphylococcus aureuselicits murine CD4+T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responsesin vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of liveStaphylococcus aureusin vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremiain vivorelative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid.

scholarly journals A New Local Variant (ST764) of the Globally Disseminated ST5 Lineage of Hospital-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) Carrying the Virulence Determinants of Community-Associated MRSA

2013 ◽  
Vol 57 (4) ◽  
pp. 1589-1595 ◽  
Author(s):  
Tomomi Takano ◽  
Wei-Chun Hung ◽  
Michiko Shibuya ◽  
Wataru Higuchi ◽  
Yasuhisa Iwao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcal Enterotoxin B ◽  
Virulence Determinants ◽  
Methicillin Resistant ◽  
Content Type ◽  
Local Variant ◽  
Invasive Infections ◽  
Enhanced Expression ◽  
Household Members ◽  
Panton Valentine Leukocidin

ABSTRACTThe ST5 lineage of methicillin-resistantStaphylococcus aureus(MRSA) is one of the most globally disseminated hospital-associated MRSA (HA-MRSA) lineages. We isolated a new local variant (designated ST764) over at least 5 years that causes invasive infections, including necrotizing fasciitis, and is carried by medical students, as well as household members. Analysis of the genome sequence of one isolate compared to that of the reference ST5 strain revealed that ST764 had acquired virulence traits similar to those of community-associated MRSA (CA-MRSA) through the acquisition of two new mobile genetic elements, ACMEII and SaPInn54, which carried ACMEarcAand the staphylococcal enterotoxin B gene (seb), respectively, and through enhanced expression of cytolytic peptide genes, although ST764 was negative for Panton-Valentine leukocidin. Other differences between ST764 and ST5 included the acquisition of an ACMEII-related cassette (cJR1), prophage φ2NN54, and streptococcal Tn5251and decreased numbers of copies of Tn554. As for superantigen genes, although the two possessedseg,sei,sem,sen, andseo, ST764 lackedtst,sec,sel, andsep. The data suggest that ST764 MRSA is a novel hybrid variant of ST5 HA-MRSA with the characteristics of CA-MRSA and that the evolution of ST764 includes multiple steps, e.g., acquisition of novel or nonstaphylococcal mobile elements.

scholarly journals RexAB Is Essential for the Mutagenic Repair of Staphylococcus aureus DNA Damage Caused by Co-trimoxazole

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Rebecca S. Clarke ◽  
Maya S. Bruderer ◽  
Kam Pou Ha ◽  
Andrew M. Edwards
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Damage ◽  
Dna Repair ◽  
Sos Response ◽  
Dependent Manner ◽  
Content Type ◽  
Sos Induction ◽  
Therapeutic Value ◽  
Emergence Of Resistance

ABSTRACT Co-trimoxazole (SXT) is a combination therapeutic that consists of sulfamethoxazole and trimethoprim that is increasingly used to treat skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the use of SXT is limited to the treatment of low-burden, superficial S. aureus infections and its therapeutic value is compromised by the frequent emergence of resistance. As a first step toward the identification of approaches to enhance the efficacy of SXT, we examined the role of bacterial DNA repair in antibiotic susceptibility and mutagenesis. We found that mutants lacking the DNA repair complex RexAB had a modest SXT MIC that was 2-fold lower than that seen with wild-type strains but were killed 50-fold to 5,000-fold more efficiently by the combination antibiotic at the breakpoint concentration. SXT-mediated DNA damage occurred via both thymidine limitation and the generation of reactive oxygen species and triggered induction of the SOS response in a RexAB-dependent manner. SOS induction was associated with a 50% increase in the mutation rate, which may contribute to emergence of resistant strains during SXT therapy. In summary, this work determined that SXT caused DNA damage in S. aureus via both thymidine limitation and oxidative stress and that the damage was repaired by the RexAB complex, leading to induction of the mutagenic SOS response. Small-molecule inhibitors of RexAB could therefore have therapeutic value by increasing the efficacy of SXT and decreasing the emergence of drug resistance during treatment of infections caused by S. aureus.

scholarly journals Association of Diverse Staphylococcus aureus Populations with Pseudomonas aeruginosa Coinfection and Inflammation in Cystic Fibrosis Airway Infection

mSphere ◽  
2021 ◽  
Author(s):  
Marie K. Wieneke ◽  
Felix Dach ◽  
Claudia Neumann ◽  
Dennis Görlich ◽  
Lena Kaese ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Therapy ◽  
Content Type ◽  
Airway Infection ◽  
Cystic Fibrosis Airway

Staphylococcus aureus can persist for extended periods in the airways of people with cystic fibrosis (CF) in spite of antibiotic therapy and high numbers of neutrophils, which fail to eradicate this pathogen. Therefore, S. aureus needs to adapt to this hostile niche.

scholarly journals Evolution of Staphylococcus aureus under Vancomycin Selective Pressure: the Role of the Small-Colony Variant Phenotype

2014 ◽  
Vol 59 (2) ◽  
pp. 1347-1351 ◽  
Author(s):  
Justin R. Lenhard ◽  
Christof von Eiff ◽  
Irene S. Hong ◽  
Patricia N. Holden ◽  
Michael D. Bear ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Selective Pressure ◽  
Type Model ◽  
Methicillin Resistant ◽  
Small Colony Variants ◽  
Content Type ◽  
Small Colony Variant ◽  
Small Colony

ABSTRACTStaphylococcus aureussmall-colony variants (SCVs) often persist despite antibiotic therapy. Against a 108-CFU/ml methicillin-resistantS. aureus(MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenichemBknockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log10CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R2> 0.90).

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