Special Issue "Staphylococcus aureus Infection and Antimicrobial Resistance"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 November 2018)

Special Issue Editor

Guest Editor
Dr. Joan Geoghegan

Department of Microbiology Moyne Institute of Preventive Medicine School of Genetics and Microbiology Trinity College Dublin, the University of Dublin Dublin 2, Ireland
Website | E-Mail
Interests: Staphylococcus aureus; bacterial adhesion; biofilm formation; virulence determinants; skin infection

Special Issue Information

Dear Colleagues,

The bacterium Staphylococcus aureus is of major public health importance globally. It is a versatile pathogen causing a range of infections, such as pneumonia, septicaemia, endocarditis, bone and joint infections and skin and soft tissue infections. This Special Issue is dedicated to “Staphylococcus aureus Infection and Antimicrobial Resistance”. Antibiotic resistance complicates the treatment of S. aureus infection and epidemic clones of methicillin resistant S. aureus (MRSA) are a major threat to human health. At present, there is substantial interest in gaining a better understanding of the pathophysiology of the bacterium to identify new strategies to treat antibiotic-resistant strains. In addition there is a need to know more about factors influencing the spread and maintenance of antibiotic resistance determinants. We invite you to submit a review article or original research article related to these topics. In particular we welcome manuscripts that provide new insights into the role of virulence factors or antibiotic resistance determinants in contributing to the success of S. aureus.

Dr. Joan Geoghegan
Guest Editor

Manuscript Submission Information

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Keywords

  • Staphylococcus aureus
  • Antibiotic resistance
  • Virulence factors
  • Methicillin-resistant S. aureus (MRSA)
  • Immune evasion
  • Colonization

Published Papers (7 papers)

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Research

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Open AccessArticle Enzymes Catalyzing the TCA- and Urea Cycle Influence the Matrix Composition of Biofilms Formed by Methicillin-Resistant Staphylococcus aureus USA300
Microorganisms 2018, 6(4), 113; https://doi.org/10.3390/microorganisms6040113
Received: 27 July 2018 / Revised: 17 October 2018 / Accepted: 25 October 2018 / Published: 29 October 2018
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Abstract
In methicillin-sensitive Staphylococcus aureus (MSSA), the tricarboxylic acid (TCA) cycle is known to negatively regulate production of the major biofilm-matrix exopolysaccharide, PIA/PNAG. However, methicillin-resistant S. aureus (MRSA) produce a primarily proteinaceous biofilm matrix, and contribution of the TCA-cycle therein remains unclear. Utilizing USA300-JE2 [...] Read more.
In methicillin-sensitive Staphylococcus aureus (MSSA), the tricarboxylic acid (TCA) cycle is known to negatively regulate production of the major biofilm-matrix exopolysaccharide, PIA/PNAG. However, methicillin-resistant S. aureus (MRSA) produce a primarily proteinaceous biofilm matrix, and contribution of the TCA-cycle therein remains unclear. Utilizing USA300-JE2 Tn-mutants (NARSA) in genes encoding TCA- and urea cycle enzymes for transduction into a prolific biofilm-forming USA300 strain (UAS391-Erys), we studied the contribution of the TCA- and urea cycle and of proteins, eDNA and PIA/PNAG, to the matrix. Genes targeted in the urea cycle encoded argininosuccinate lyase and arginase (argH::Tn and rocF::Tn), and in the TCA-cycle encoded succinyl-CoA synthetase, succinate dehydrogenase, aconitase, isocitrate dehydrogenase, fumarate hydratase class II, and citrate synthase II (sucC::Tn, sdhA/B::Tn, acnA::Tn, icd::Tn, fumC::Tn and gltA::Tn). Biofilm formation was significantly decreased under no flow and flow conditions by argH::Tn, fumC::Tn, and sdhA/B::Tn (range OD492 0.374−0.667; integrated densities 2.065−4.875) compared to UAS391-EryS (OD492 0.814; integrated density 10.676) (p ≤ 0.008). Cellular and matrix stains, enzymatic treatment (Proteinase K, DNase I), and reverse-transcriptase PCR-based gene-expression analysis of fibronectin-binding proteins (fnbA/B) and the staphylococcal accessory regulator (sarA) on pre-formed UAS391-Erys and Tn-mutant biofilms showed: (i) < 1% PIA/PNAG in the proteinaceous/eDNA matrix; (ii) increased proteins under no flow and flow in the matrix of Tn mutant biofilms (on average 50 and 51 (±11)%) compared to UAS391-Erys (on average 22 and 25 (±4)%) (p < 0.001); and (iii) down- and up-regulation of fnbA/B and sarA, respectively, in Tn-mutants compared to UAS391-EryS (0.62-, 0.57-, and 2.23-fold on average). In conclusion, we show that the biofilm matrix of MRSA-USA300 and the corresponding Tn mutants is PIA/PNAG-independent and are mainly composed of proteins and eDNA. The primary impact of TCA-cycle inactivation was on the protein component of the biofilm matrix of MRSA-USA300. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
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Open AccessArticle World-Wide Variation in Incidence of Staphylococcus aureus Associated Ventilator-Associated Pneumonia: A Meta-Regression
Microorganisms 2018, 6(1), 18; https://doi.org/10.3390/microorganisms6010018
Received: 19 January 2018 / Revised: 13 February 2018 / Accepted: 25 February 2018 / Published: 27 February 2018
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Abstract
Staphylococcus aureus (S. aureus) is a common Ventilator-Associated Pneumonia (VAP) isolate. The objective here is to define the extent and possible reasons for geographic variation in the incidences of S. aureus-associated VAP, MRSA-VAP and overall VAP. A meta-regression model of [...] Read more.
Staphylococcus aureus (S. aureus) is a common Ventilator-Associated Pneumonia (VAP) isolate. The objective here is to define the extent and possible reasons for geographic variation in the incidences of S. aureus-associated VAP, MRSA-VAP and overall VAP. A meta-regression model of S. aureus-associated VAP incidence per 1000 Mechanical Ventilation Days (MVD) was undertaken using random effects methods among publications obtained from a search of the English language literature. This model incorporated group level factors such as admission to a trauma ICU, year of publication and use of bronchoscopic sampling towards VAP diagnosis. The search identified 133 publications from seven worldwide regions published over three decades. The summary S. aureus-associated VAP incidence was 4.5 (3.9–5.3) per 1000 MVD. The highest S. aureus-associated VAP incidence is amongst reports from the Mediterranean (mean; 95% confidence interval; 6.1; 4.1–8.5) versus that from Asian ICUs (2.1; 1.5–3.0). The incidence of S. aureus-associated VAP varies by up to three-fold (for the lowest versus highest incidence) among seven geographic regions worldwide, whereas the incidence of VAP varies by less than two-fold. Admission to a trauma unit is the most important group level correlate for S. aureus-associated VAP. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
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Open AccessArticle Unusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base
Microorganisms 2018, 6(1), 2; https://doi.org/10.3390/microorganisms6010002
Received: 7 December 2017 / Revised: 29 December 2017 / Accepted: 2 January 2018 / Published: 4 January 2018
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Abstract
Selective digestive decontamination (SDD, topical antibiotic regimens applied to the respiratory tract) appears effective for preventing ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients. However, potential contextual effects of SDD on Staphylococcus aureus infections in the ICU remain unclear. The S. [...] Read more.
Selective digestive decontamination (SDD, topical antibiotic regimens applied to the respiratory tract) appears effective for preventing ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients. However, potential contextual effects of SDD on Staphylococcus aureus infections in the ICU remain unclear. The S. aureus ventilator associated pneumonia (S. aureus VAP), VAP overall and S. aureus bacteremia incidences within component (control and intervention) groups within 27 SDD studies were benchmarked against 115 observational groups. Component groups from 66 studies of various interventions other than SDD provided additional points of reference. In 27 SDD study control groups, the mean S. aureus VAP incidence is 9.6% (95% CI; 6.9–13.2) versus a benchmark derived from 115 observational groups being 4.8% (95% CI; 4.2–5.6). In nine SDD study control groups the mean S. aureus bacteremia incidence is 3.8% (95% CI; 2.1–5.7) versus a benchmark derived from 10 observational groups being 2.1% (95% CI; 1.1–4.1). The incidences of S. aureus VAP and S. aureus bacteremia within the control groups of SDD studies are each higher than literature derived benchmarks. Paradoxically, within the SDD intervention groups, the incidences of both S. aureus VAP and VAP overall are more similar to the benchmarks. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
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Review

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Open AccessReview Messing with the Sentinels—The Interaction of Staphylococcus aureus with Dendritic Cells
Microorganisms 2018, 6(3), 87; https://doi.org/10.3390/microorganisms6030087
Received: 6 July 2018 / Revised: 12 August 2018 / Accepted: 14 August 2018 / Published: 15 August 2018
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Abstract
Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent colonizer, threatening human health worldwide. Protection against S. aureus infection is challenging, as the bacteria have sophisticated strategies to escape the host immune response. To maintain equilibrium with [...] Read more.
Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent colonizer, threatening human health worldwide. Protection against S. aureus infection is challenging, as the bacteria have sophisticated strategies to escape the host immune response. To maintain equilibrium with S. aureus, both innate and adaptive immune effector mechanisms are required. Dendritic cells (DCs) are critical players at the interface between the two arms of the immune system, indispensable for inducing specific T cell responses. In this review, we highlight the importance of DCs in mounting innate as well as adaptive immune responses against S. aureus with emphasis on their role in S. aureus-induced respiratory diseases. We also review what is known about mechanisms that S. aureus has adopted to evade DCs or manipulate these cells to its advantage. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
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Open AccessReview PBP4: A New Perspective on Staphylococcus aureus β-Lactam Resistance
Microorganisms 2018, 6(3), 57; https://doi.org/10.3390/microorganisms6030057
Received: 30 May 2018 / Revised: 19 June 2018 / Accepted: 20 June 2018 / Published: 22 June 2018
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Abstract
β-lactam antibiotics are excellent drugs for treatment of staphylococcal infections, due to their superior efficacy and safety compared to other drugs. Effectiveness of β-lactams is severely compromised due to resistance, which is widespread among clinical strains of Staphylococcus aureus. β-lactams inhibit bacterial [...] Read more.
β-lactam antibiotics are excellent drugs for treatment of staphylococcal infections, due to their superior efficacy and safety compared to other drugs. Effectiveness of β-lactams is severely compromised due to resistance, which is widespread among clinical strains of Staphylococcus aureus. β-lactams inhibit bacterial cells by binding to penicillin binding proteins (PBPs), which perform the penultimate steps of bacterial cell wall synthesis. Among PBPs of S. aureus, PBP2a has received the most attention for the past several decades due to its preeminent role in conferring both high-level and broad-spectrum resistance to the entire class of β-lactam drugs. Studies on PBP2a have thus unraveled incredible details of its mechanism of action. We have recently identified that an uncanonical, low molecular weight PBP of S. aureus, PBP4, can also provide high-level and broad-spectrum resistance to the entire class of β-lactam drugs at a level similar to that of PBP2a. The role of PBP4 has typically been considered not so important for β-lactam resistance of S. aureus, and as a result its mode of action remains largely unknown. In this article, we review our current knowledge of PBP4 mediating β-lactam resistance in S. aureus. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
Open AccessReview Pediatric Methicillin-Resistant Staphylococcus aureus Osteoarticular Infections
Microorganisms 2018, 6(2), 40; https://doi.org/10.3390/microorganisms6020040
Received: 13 March 2018 / Revised: 27 April 2018 / Accepted: 27 April 2018 / Published: 4 May 2018
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Abstract
Osteoarticular infections (OSI) are a significant cause of hospitalizations and morbidity in young children. The pediatric patient with OSI presents unique challenges in diagnosis and management due to higher morbidity, effect on growth plate with associated long-lasting sequelae, and challenges in early identification [...] Read more.
Osteoarticular infections (OSI) are a significant cause of hospitalizations and morbidity in young children. The pediatric patient with OSI presents unique challenges in diagnosis and management due to higher morbidity, effect on growth plate with associated long-lasting sequelae, and challenges in early identification and management. Methicillin-resistant Staphylococcus aureus (MRSA), first described in the 1960s, has evolved rapidly to emerge as a predominant cause of OSI in children, and therefore empiric treatment for OSI should include an antibiotic effective against MRSA. Characterizing MRSA strains can be done by antimicrobial susceptibility testing, detection of Panton–Valentine leukocidin (PVL) gene, staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Worldwide, community-onset methicillin-resistant staphylococcal disease is widespread and is mainly associated with a PVL-producing clone, ST8/USA300. Many studies have implied a correlation between PVL genes and more severe infection. We review MRSA OSI along with the pertinent aspects of its pathogenesis, clinical spectrum, diagnosis, and current guidelines for management. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
Open AccessReview Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases
Microorganisms 2018, 6(1), 25; https://doi.org/10.3390/microorganisms6010025
Received: 13 February 2018 / Revised: 8 March 2018 / Accepted: 11 March 2018 / Published: 13 March 2018
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Abstract
Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of [...] Read more.
Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. Full article
(This article belongs to the Special Issue Staphylococcus aureus Infection and Antimicrobial Resistance)
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