Special Issue "Staphylococci Antimicrobial Resistance"

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (30 June 2019).

Special Issue Editor

Prof. Dr. John E. Gustafson
E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, 246C Noble Research Center, Oklahoma State University, Stillwater, OK 74078-3035, USA
Interests: antibiotic resistance; the effects of essential oils/antiseptics/disinfectants on bacteria; Staphylococcus aureus; Elizabethkingia
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The staphylococci are worthy adversaries that deserve our undivided attention. In particular, the ability of the staphylococci to acquire resistance to antimicrobials via horizontal gene transfer and mutation will remain a direct threat until a biological breakthrough occurs that replaces traditional antimicrobial therapies, or new vaccines emerge that can be used to prevent and cure diseases caused by these organisms. These organisms also display an intrinsic level of resistance/susceptibility to all antimicrobials that requires a large collection of genes and gene products, a responsive metabolism, and a robust finely-tuned cross-protective stress response mechanism. In turn, many of these intrinsic factors act as “scaffolding” that allow clinically-relevant antimicrobial resistance genes and mutations to be fully expressed by these organisms. The application of “omics” technology to better understand staphylococcal antimicrobial resistance mechanisms continues to reinforce this concept. A great deal of research also continues to reveal the unique evolutionary trajectories of these pathogens and the epidemiology of specific antimicrobial-resistant and -susceptible strains that cause human and animal infections. This Special Issue seeks manuscript submissions that further our understanding of antimicrobial resistance in the staphylococci. Submissions on the response of these organisms to antiseptics/disinfectants/biocides which are used to reduce transmission of these organisms are especially encouraged.

Prof. Dr. John E. Gustafson
Guest Editor

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Keywords

  • MRSA
  • VISA
  • Staphylococci
  • antimicrobial resistance
  • disinfectant and antiseptic reduced susceptibility
  • epidemiology
  • genomics

Published Papers (12 papers)

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Research

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Article
Proteomic and Metabolomic Analyses of a Tea-Tree Oil-Selected Staphylococcus aureus Small Colony Variant
Antibiotics 2019, 8(4), 248; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8040248 - 03 Dec 2019
Viewed by 1602
Abstract
Tea tree oil (TTO) is hypothesized to kill bacteria by indiscriminately denaturing membrane and protein structures. A Staphylococcus aureus small colony variant (SCV) selected with TTO (SH1000-TTORS-1) demonstrated slowed growth, reduced susceptibility to TTO, a diminutive cell size, and a thinned cell wall. [...] Read more.
Tea tree oil (TTO) is hypothesized to kill bacteria by indiscriminately denaturing membrane and protein structures. A Staphylococcus aureus small colony variant (SCV) selected with TTO (SH1000-TTORS-1) demonstrated slowed growth, reduced susceptibility to TTO, a diminutive cell size, and a thinned cell wall. Utilizing a proteomics and metabolomics approach, we have now revealed that the TTO-selected SCV mutant demonstrated defective fatty acid synthesis, an alteration in the expression of genes and metabolites associated with central metabolism, the induction of a general stress response, and a reduction of proteins critical for active growth and translation. SH1000-TTORS-1 also demonstrated an increase in amino acid accumulation and a decrease in sugar content. The reduction in glycolytic pathway proteins and sugar levels indicated that carbon flow through glycolysis and gluconeogenesis is reduced in SH1000-TTORS-1. The increase in amino acid accumulation coincides with the reduced production of translation-specific proteins and the induction of proteins associated with the stringent response. The decrease in sugar content likely deactivates catabolite repression and the increased amino acid pool observed in SH1000-TTORS-1 represents a potential energy and carbon source which could maintain carbon flow though the tricarboxylic acid (TCA) cycle. It is noteworthy that processes that contribute to the production of the TTO targets (proteins and membrane) are reduced in SH1000-TTORS-1. This is one of a few studies describing a mechanism that bacteria utilize to withstand the action of an antiseptic which is thought to inactivate multiple cellular targets. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Article
Proteomic and Membrane Lipid Correlates of Re-duced Host Defense Peptide Susceptibility in a snoD Mutant of Staphylococcus aureus
Antibiotics 2019, 8(4), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8040169 - 28 Sep 2019
Cited by 1 | Viewed by 1300
Abstract
We previously described a transposon mutant in Staphylococcus aureus strain SH1000 that exhibited reduced susceptibility to cationic thrombin-induced platelet microbicidal proteins (tPMPs). The transposon insertion site was mapped to the gene snoD, the staphylococcal nuo orthologue. Hence, further studies have been performed [...] Read more.
We previously described a transposon mutant in Staphylococcus aureus strain SH1000 that exhibited reduced susceptibility to cationic thrombin-induced platelet microbicidal proteins (tPMPs). The transposon insertion site was mapped to the gene snoD, the staphylococcal nuo orthologue. Hence, further studies have been performed to understand how this mutation impacts susceptibility to tPMP, by comparing proteomics profiling and membrane lipid analyses of the parent vs. mutant strains. Surprisingly, the mutant showed differential regulation of only a single protein when cultivated aerobically (FadB), and only a small number of proteins under anaerobic growth conditions (AdhE, DapE, Ddh, Ald1, IlvA1, AgrA, Rot, SA2366, and SA2367). Corresponding to FadB impact on lipid remodeling, membrane fatty acid analyses showed that the snoD mutant contained more short chain anteiso-, but fewer short chain iso-branched chain fatty acids under both aerobic and anaerobic conditions vs. the parental strain. Based upon these proteomic and membrane compositional data, a hypothetical “network” model was developed to explain the impact of the snoD mutation upon tPMP susceptibility. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Article
Intermittent colonisation with Methicillin-Resistant Staphylococcal aureus can be eradicated from the Airways of Adults with Cystic Fibrosis
Antibiotics 2019, 8(3), 113; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030113 - 09 Aug 2019
Cited by 1 | Viewed by 1192
Abstract
The airways of people with cystic fibrosis (CF) are chronically colonised with different pathogens. With recent interest in methicillin-resistant Staphylococcus aureus (MRSA), we have recently examined the rates of MRSA colonisation in different groups within our CF Service. This paper now examines the [...] Read more.
The airways of people with cystic fibrosis (CF) are chronically colonised with different pathogens. With recent interest in methicillin-resistant Staphylococcus aureus (MRSA), we have recently examined the rates of MRSA colonisation in different groups within our CF Service. This paper now examines the effectiveness of eradication strategies to clear the MRSA colonisation. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
Article
Comparison of Antibiotic Resistance Profile and Biofilm Production of Staphylococcus aureus Isolates Derived from Human Specimens and Animal-Derived Samples
Antibiotics 2019, 8(3), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030097 - 19 Jul 2019
Cited by 10 | Viewed by 1992
Abstract
Background: The diffusion of antimicrobial resistance is a significant concern for public health worldwide. Staphylococcus aureus represents a paradigm microorganism for antibiotic resistance in that resistant strains appear within a decade after the introduction of new antibiotics. Methods: Fourteen S. aureus isolates from [...] Read more.
Background: The diffusion of antimicrobial resistance is a significant concern for public health worldwide. Staphylococcus aureus represents a paradigm microorganism for antibiotic resistance in that resistant strains appear within a decade after the introduction of new antibiotics. Methods: Fourteen S. aureus isolates from human specimens and twenty-one from samples of animal origin, were compared for their antimicrobial resistance and biofilm capability. In addition, they were characterized at the molecular level to detect the antimicrobial resistance mecA gene and genes related with enterotoxin, toxin, and biofilm production. Results: Both phenotypic and molecular analysis showed main differences among human- and animal-derived isolates. Among the human-derived isolates, more multidrug-resistant isolates were detected and mecA gene, enterotoxin, and toxin genes were more prevalent. Different genes involved in biofilm production were detected with bap present only in animal-derived isolates and sasC present in both isolates, however, with a higher prevalence in the human-derived isolates. Biofilm capability was higher in human-derived isolates mainly associated to the sasC gene. Conclusions: The overall results indicate that human S. aureus isolates are more virulent and resistant than the isolates of animal origin randomly selected with no infection anamnesis. This study confirms that selection for more virulent and resistant S. aureus strains is related to the clinical practice. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Article
Impact of Mobility on Methicillin-Resistant Staphylococcus aureus among Injection Drug Users
Antibiotics 2019, 8(2), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020081 - 17 Jun 2019
Viewed by 1650
Abstract
In this study, we develop and present a deterministic model for the transmission dynamics of methicillin-resistant staphylococcus aureus (MRSA) among injection drug users. The model consists of non-injection drug users as well as low-and high-risk injection drug users (IDUs). The model further incorporates [...] Read more.
In this study, we develop and present a deterministic model for the transmission dynamics of methicillin-resistant staphylococcus aureus (MRSA) among injection drug users. The model consists of non-injection drug users as well as low-and high-risk injection drug users (IDUs). The model further incorporates the movement of these individuals between large metro, suburban and rural areas. The model parameters were estimated by fitting the model to the 2008–2013 disease prevalence data for non-IDUs obtained from the Agency for Healthcare and Research and Quality (AHRQ), as well as the 2009–2013 Census Bureau data for the number of individuals migrating between three different counties in Kansas. Sensitivity analysis was implemented to determine the parameters with the most significant impact on the total number of infected individuals; the transmission probability, recovery rates, and positive behavioral change parameter for the subgroup have the most significant effect on the number of infected individuals. Furthermore, the sensitivity of the parameters in the different areas was the same when the areas are disconnected. When the areas are connected, the parameters in large-metro areas were the most sensitive, and the rural areas were least sensitive. The result shows that to effectively control the disease across the large metro, suburban and rural areas, it is best to focus on controlling both behavior and disease in the large metro area as this has a trickle-down effect to the other places. However, controlling behavior and disease at the same time in all the areas will lead to the elimination of the disease. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Article
Identification of Small Molecule Inhibitors of Staphylococcus aureus RnpA
Antibiotics 2019, 8(2), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020048 - 28 Apr 2019
Cited by 3 | Viewed by 2275
Abstract
Staphylococcus aureus RnpA is thought to be a unique dual functional antimicrobial target that is required for two essential cellular processes, precursor tRNA processing and messenger RNA degradation. Herein, we used a previously described whole cell-based mupirocin synergy assay to screen members of [...] Read more.
Staphylococcus aureus RnpA is thought to be a unique dual functional antimicrobial target that is required for two essential cellular processes, precursor tRNA processing and messenger RNA degradation. Herein, we used a previously described whole cell-based mupirocin synergy assay to screen members of a 53,000 compound small molecule diversity library and simultaneously enrich for agents with cellular RnpA inhibitory activity. A medicinal chemistry-based campaign was launched to generate a preliminary structure activity relationship and guide early optimization of two novel chemical classes of RnpA inhibitors identified, phenylcarbamoyl cyclic thiophene and piperidinecarboxamide. Representatives of each chemical class displayed potent anti-staphylococcal activity, limited the protein’s in vitro ptRNA processing and mRNA degradation activities, and exhibited favorable therapeutic indexes. The most potent piperidinecarboxamide RnpA inhibitor, JC2, displayed inhibition of cellular RnpA mRNA turnover, RnpA-depletion strain hypersusceptibility, and exhibited antimicrobial efficacy in a wax worm model of S. aureus infection. Taken together, these results establish that the whole cell screening assay used is amenable to identifying small molecule RnpA inhibitors within large chemical libraries and that the chemical classes identified here may represent progenitors of new classes of antimicrobials that target RnpA. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Article
Prevalence of Methicillin-Resistant Staphylococcus sp. (MRS) in Different Companion Animals and Determination of Risk Factors for Colonization with MRS
Antibiotics 2019, 8(2), 36; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020036 - 05 Apr 2019
Cited by 14 | Viewed by 2114
Abstract
The aim of this study was to detect the prevalence of methicillin-resistant Staphylococcus sp. (MRS) in populations of companion animals that either have previously been exposed or have not been exposed to antibiotic therapy or veterinary facilities, and if owners’ healthcare profession had [...] Read more.
The aim of this study was to detect the prevalence of methicillin-resistant Staphylococcus sp. (MRS) in populations of companion animals that either have previously been exposed or have not been exposed to antibiotic therapy or veterinary facilities, and if owners’ healthcare profession had an influence on colonization with MRS. In addition, the antimicrobial resistance pheno- and genotype were investigated and risks for colonization with MRS were assessed. During this study, 347 nasal swabs (dogs n = 152; cats n = 107; rabbits n = 88) were investigated for the presence of methicillin-resistant Staphylococcus aureus (MRSA). In addition, 131 nasal swabs (dogs n = 79; cats n = 47; rabbits = 3; guinea pigs = 2) were examined for the presence of MRSA but also other MRS. In total, 23 MRS isolates belonged to nine staphylococcal species: Staphylococcus epidermidis (n = 11), Staphylococcus warneri (n = 3), Staphylococcus hominis (n = 2), Staphylococcus pseudintermedius (n = 2), and singletons Staphylococcus cohnii, Staphylococcus sciuri, Staphylococcus fleurettii, Staphylococcus lentus, and Staphylococcus haemolyticus. Twenty isolates displayed a multidrug-resistant phenotype. Various resistance and biocide resistance genes were detected among the examined staphylococci. Risk assessment for MRS colonization was conducted using a number of factors, including animal species, breed, age, gender, recent veterinary health care hospitalization, and antibiotic prescription, resulting in recent veterinary health care hospitalization being a significant risk factor. The detection of multidrug-resistant MRS in healthy animals is of importance due to their zoonotic potential. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)

Review

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Review
Methods Used for the Eradication of Staphylococcal Biofilms
Antibiotics 2019, 8(4), 174; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8040174 - 04 Oct 2019
Cited by 5 | Viewed by 2430
Abstract
Staphylococcus aureus is considered one of the leading pathogens responsible for community and healthcare-associated infections. Among them, infections caused by methicillin-resistant strains (MRSA) are connected with ineffective or prolonged treatment. The therapy of staphylococcal infections faces many difficulties, not only because of the [...] Read more.
Staphylococcus aureus is considered one of the leading pathogens responsible for community and healthcare-associated infections. Among them, infections caused by methicillin-resistant strains (MRSA) are connected with ineffective or prolonged treatment. The therapy of staphylococcal infections faces many difficulties, not only because of the bacteria’s resistance to antibiotics and the multiplicity of virulence factors it produces, but also due to its ability to form a biofilm. The present review focuses on several approaches used for the assessment of staphylococcal biofilm eradication. The methods described here are successfully applied in research on the prevention of biofilm-associated infections, as well as in their management. They include not only the evaluation of the antimicrobial activity of novel compounds, but also the methods for biomaterial functionalization. Moreover, the advantages and limitations of different dyes and techniques used for biofilm characterization are discussed. Therefore, this review may be helpful for those scientists who work on the development of new antistaphylococcal compounds. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Review
Staphylococcus aureus Infections in Malaysia: A Review of Antimicrobial Resistance and Characteristics of the Clinical Isolates, 1990–2017
Antibiotics 2019, 8(3), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030128 - 26 Aug 2019
Cited by 8 | Viewed by 2356
Abstract
Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last [...] Read more.
Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last resort, gives a great challenge to the treatment and management of MRSA infections. While vancomycin resistance among Malaysian MRSA isolates has yet to be documented, a case of vancomycin resistant S. aureus has been reported in our neighboring country, Indonesia. In this review, we present the antimicrobial resistance profiles of S. aureus clinical isolates in Malaysia with data obtained from the Malaysian National Surveillance on Antimicrobial Resistance (NSAR) reports as well as various peer-reviewed published records spanning a period of nearly three decades (1990–2017). We also review the clonal types and characteristics of Malaysian S. aureus isolates, where hospital-associated (HA) MRSA isolates tend to carry staphylococcal cassette chromosome mec (SCCmec) type III and were of sequence type (ST)239, whereas community-associated (CA) isolates are mostly SCCmec type IV/V and ST30. More comprehensive surveillance data that include molecular epidemiological data would enable further in-depth understanding of Malaysian S. aureus isolates. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Review
Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection
Antibiotics 2019, 8(2), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020071 - 29 May 2019
Cited by 4 | Viewed by 2558
Abstract
Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and [...] Read more.
Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Review
Intracellular Penetration and Effects of Antibiotics on Staphylococcus aureus Inside Human Neutrophils: A Comprehensive Review
Antibiotics 2019, 8(2), 54; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020054 - 04 May 2019
Cited by 16 | Viewed by 2159
Abstract
Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction [...] Read more.
Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction and intracellular infection are immune-deficient patients or, as has recently been described, severely injured patients. These dysfunctional neutrophils can become hide-out spots or “Trojan horses” for S. aureus. This location offers protection to bacteria from most antibiotics and allows transportation of bacteria throughout the body inside moving neutrophils. When neutrophils die, these bacteria are released at different locations. In this review, we therefore focus on the capacity of several groups of antibiotics to enter human neutrophils, kill intracellular S. aureus and affect neutrophil function. We provide an overview of intracellular capacity of available antibiotics to aid in clinical decision making. In conclusion, quinolones, rifamycins and sulfamethoxazole-trimethoprim seem very effective against intracellular S. aureus in human neutrophils. Oxazolidinones, macrolides and lincosamides also exert intracellular antibiotic activity. Despite that the reviewed data are predominantly of in vitro origin, these findings should be taken into account when intracellular infection is suspected, as can be the case in severely injured patients. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
Review
The Continuing Threat of Methicillin-Resistant Staphylococcus aureus
Antibiotics 2019, 8(2), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8020052 - 02 May 2019
Cited by 68 | Viewed by 4311
Abstract
Staphylococcus aureus has been an exceptionally successful pathogen, which is still relevant in modern age-medicine due to its adaptability and tenacity. This bacterium may be a causative agent in a plethora of infections, owing to its abundance (in the environment and in the [...] Read more.
Staphylococcus aureus has been an exceptionally successful pathogen, which is still relevant in modern age-medicine due to its adaptability and tenacity. This bacterium may be a causative agent in a plethora of infections, owing to its abundance (in the environment and in the normal flora) and the variety of virulence factors that it possesses. Methicillin-resistant S. aureus (MRSA) strains—first described in 1961—are characterized by an altered penicillin-binding protein (PBP2a/c) and resistance to all penicillins, cephalosporins, and carbapenems, which makes the β-lactam armamentarium clinically ineffective. The acquisition of additional resistance determinants further complicates their eradication; therefore, MRSA can be considered as the first representative of multidrug-resistant bacteria. Based on 230 references, the aim of this review is to recap the history, the emergence, and clinical features of various MRSA infections (hospital-, community-, and livestock-associated), and to summarize the current advances regarding MRSA screening, typing, and therapeutic options (including lipoglycopeptides, oxazolidinones, anti-MRSA cephalosporins, novel pleuromutilin-, tetracycline- and quinolone-derivatives, daptomycin, fusidic acid, in addition to drug candidates in the development phase), both for an audience of clinical microbiologists and infectious disease specialists. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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