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Antibiotics
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Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus
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Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus

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 (1 October 2021) | Viewed by 25947

Special Issue Editors

Dr. Jhih-Hang Jiang

E-Mail Website
Guest Editor
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia
Interests: antimicrobials and resistance mechanisms; Staphylocococcus aureus; host immune responses
Dr. Xenia Kostoulias

E-Mail Website
Guest Editor
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia
Interests: antimicrobial resistance; bacterial virulence; biofilms; Staphylococcus aureus; Acinetobacter baumannii

Special Issue Information

Dear Colleagues,

Since their discovery, antibiotics have revolutionsed medicine, resulting in a major decline in infection related morbidity and mortality. In the last eight decades, the widespread use of antibiotics, has resulted in the emergence of antimicrobial resistance (AMR). With a post-antibiotic era fast approaching, the rapid rise of AMR has now become one of the greatest threats to human health. Staphylococcus aureus is particularly concerning as it has both an arsenal of virulence factors as well as the ability to acquire resistance to most antibiotics. The clinical use of methicillin has led to the appearance of methicillin resistant S. aureus (MRSA), not only in the traditional clinical setting but also in the community setting, leading to infections in people without predisposing risk factors. Treatment of MRSA infections increasingly relies on last resort antibiotics but further resistance to the last line antibiotics is alarming.

Elucidating the molecular mechanisms behind these complex resistance phenotypes is crucial for novel therapeutic strategies that can circumvent AMR development. Application of new technology such as next-generation sequencing and cryo-eletron microscopy also provides valuable insights into AMR. In this Special Issue we seek manuscript submissions that further our undertanding of the molecular mechanisms of resistance in staphylococci. Submissions addressing resistance to non-pharmaceutical treatments such as phage therapy are also welcomed.

Dr. Jhih-Hang Jiang
Dr. Xenia Kostoulias
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic resistance
  • comparative genomics
  • biofilm
  • bacterial virulence
  • host immune responses

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Published Papers (4 papers)

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Research

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11 pages, 1728 KiB  
Article
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant Staphylococcus aureus
by Maite Villanueva, Melanie Roch, Iñigo Lasa, Adriana Renzoni and William L. Kelley
Antibiotics 2021, 10(7), 821; https://doi.org/10.3390/antibiotics10070821 - 6 Jul 2021
Cited by 5 | Viewed by 2970
Abstract
Methicillin-resistant Staphylococcus aureus infections are a global health problem. New control strategies, including fifth-generation cephalosporins such as ceftaroline, have been developed, however rare sporadic resistance has been reported. Our study aimed to determine whether disruption of two-component environmental signal systems detectably led to [...] Read more.
Methicillin-resistant Staphylococcus aureus infections are a global health problem. New control strategies, including fifth-generation cephalosporins such as ceftaroline, have been developed, however rare sporadic resistance has been reported. Our study aimed to determine whether disruption of two-component environmental signal systems detectably led to enhanced susceptibility to ceftaroline in S. aureus CA-MRSA strain MW2 at sub-MIC concentrations where cells normally continue to grow. A collection of sequential mutants in all fifteen S. aureus non-essential two-component systems (TCS) was first screened for ceftaroline sub-MIC susceptibility, using the spot population analysis profile method. We discovered a role for both ArlRS and VraSR TCS as determinants responsible for MW2 survival in the presence of sub-MIC ceftaroline. Subsequent analysis showed that dual disruption of both arlRS and vraSR resulted in a very strong ceftaroline hypersensitivity phenotype. Genetic complementation analysis confirmed these results and further revealed that arlRS and vraSR likely regulate some common pathway(s) yet to be determined. Our study shows that S. aureus uses particular TCS environmental sensing systems for this type of defense and illustrates the proof of principle that if these TCS were inhibited, the efficacy of certain antibiotics might be considerably enhanced. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus)
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11 pages, 1733 KiB  
Article
Comparison of Antivirulence Activities of Black Ginseng against Methicillin-Resistant Staphylococcus aureus According to the Number of Repeated Steaming and Drying Cycles
by Young-Seob Lee, Kwan-Woo Kim, Dahye Yoon, Geum-Soog Kim, Dong-Yeul Kwon, Ok-Hwa Kang and Dae Young Lee
Antibiotics 2021, 10(6), 617; https://doi.org/10.3390/antibiotics10060617 - 21 May 2021
Cited by 6 | Viewed by 2480
Abstract
Korean ginseng has been widely used in Eastern medicine for thousands of years. The contents of the compounds in ginseng roots change depending on the amount of steaming and drying, and the drying method used. Black ginseng (BG) is the Korean ginseng processed [...] Read more.
Korean ginseng has been widely used in Eastern medicine for thousands of years. The contents of the compounds in ginseng roots change depending on the amount of steaming and drying, and the drying method used. Black ginseng (BG) is the Korean ginseng processed by repeated steaming and drying. In this study, 5-year-old fresh Korean ginseng roots were steamed and dried 3 or 5 times, and we investigated how many cycles of steaming and drying are preferable for antivirulence activities against methicillin-resistant Staphylococcus aureus (MRSA). As a result, the antivirulence activities was increased by the treatment of BG that was steamed and dried three times, and the effect was further increased by five-time processed BG. Moreover, an ELISA showed that the TNF-α production of RAW264.7 cells stimulated by MRSA supernatants was inhibited by subinhibitory concentrations of BG extract. The expression of Hla, staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB), an important virulence factor in the pathogenicity of MRSA, was found to decrease when bacterial cells were treated with BG extract. The antivirulence activities of BG were not simply due to pathogen growth inhibition; the BG extract was shown to decrease agrA, hla, sea, and seb expression in MRSA. Therefore, BG strongly reduces the secretion of the virulence factors produced by Staphylococcus aureus, suggesting that a BG-based structure may be used for the development of drugs aimed at staphylococcal virulence-related exoproteins. This study suggests that BG could be used as a promising natural compound in the food and pharmaceutical industry. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus)
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Review

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22 pages, 1116 KiB  
Review
The Influence of Antibiotic Resistance on Innate Immune Responses to Staphylococcus aureus Infection
by Nazneen Jahan, Timothy Patton and Meredith O’Keeffe
Antibiotics 2022, 11(5), 542; https://doi.org/10.3390/antibiotics11050542 - 19 Apr 2022
Cited by 4 | Viewed by 4104
Abstract
Staphylococcus aureus (S. aureus) causes a broad range of infections and is associated with significant morbidity and mortality. S. aureus produces a diverse range of cellular and extracellular factors responsible for its invasiveness and ability to resist immune attack. In recent [...] Read more.
Staphylococcus aureus (S. aureus) causes a broad range of infections and is associated with significant morbidity and mortality. S. aureus produces a diverse range of cellular and extracellular factors responsible for its invasiveness and ability to resist immune attack. In recent years, increasing resistance to last-line anti-staphylococcal antibiotics daptomycin and vancomycin has been observed. Resistant strains of S. aureus are highly efficient in invading a variety of professional and nonprofessional phagocytes and are able to survive inside host cells. Eliciting immune protection against antibiotic-resistant S. aureus infection is a global challenge, requiring both innate and adaptive immune effector mechanisms. Dendritic cells (DC), which sit at the interface between innate and adaptive immune responses, are central to the induction of immune protection against S. aureus. However, it has been observed that S. aureus has the capacity to develop further antibiotic resistance and acquire increased resistance to immunological recognition by the innate immune system. In this article, we review the strategies utilised by S. aureus to circumvent antibiotic and innate immune responses, especially the interaction between S. aureus and DC, focusing on how this relationship is perturbed with the development of antibiotic resistance. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus)
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23 pages, 4806 KiB  
Review
Mechanisms of Resistance to Macrolide Antibiotics among Staphylococcus aureus
by Maria Miklasińska-Majdanik
Antibiotics 2021, 10(11), 1406; https://doi.org/10.3390/antibiotics10111406 - 17 Nov 2021
Cited by 58 | Viewed by 14248
Abstract
Methicillin resistant Staphylococcus aureus strains pose a serious treatment problem because of their multi-drug resistance (MDR). In staphylococcal strains, resistance to macrolides, lincosamides, and streptogramin B (MLSB) correlates with resistance to methicillin. The rapid transmission of erm genes responsible for MLS [...] Read more.
Methicillin resistant Staphylococcus aureus strains pose a serious treatment problem because of their multi-drug resistance (MDR). In staphylococcal strains, resistance to macrolides, lincosamides, and streptogramin B (MLSB) correlates with resistance to methicillin. The rapid transmission of erm genes responsible for MLSB resistance has strongly limited the clinical application of traditional macrolides such as erythromycin. On the other hand, in the age of increasing insensitivity to antibiotics the idea of implementing a therapy based on older generation drugs brings hope that the spread of antibiotic resistance will be limited. A thorough understanding of the resistance mechanisms contributes to design of antibiotics that avoid bacterial insensitivity. This review highlights the mechanisms of action of macrolides and mechanism of resistance to these antibiotics among Staphylococcus aureus. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Antibiotic Resistance in Staphylococcus aureus)
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