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Special Issue "Staphylococcus aureus Infection: Pathogenesis, Antimicrobial Resistance and Diagnostics"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2021).

Special Issue Editor

Prof. Dr. Giovanni Gherardi
E-Mail Website
Guest Editor
Department of Medicine, Campus Biomedico University, Via Alvaro del Portillo 200, 00128 Rome, Italy
Interests: antibiotic resistance; molecular typing; streptococcus; diagnostic microbiological methods; blood culture
Special Issues and Collections in MDPI journals

Special Issue Information

Dear colleagues,

Staphylococcus aureus, a Gram-positive, coagulase-positive pathogen belonging to the family Staphylococcaceae, with a spherical shape that forms grape-like clusters, is a commensal that is often present asymptomatically on parts of the human body. S. aureus is also a major human pathogen able to adapt to diverse hosts and environmental conditions, as well as to cause plenty of infections and is one of the major causes of hospital and community-acquired infections. It can cause infections of the bloodstream, skin and soft tissues, and lower respiratory tract, infections related to medical instrumentation, such as central-line associated bloodstream infection (CLABSI), and some serious deep-seated infections such as osteomyelitis and endocarditis. S. aureus is equipped with a collection of virulence factors and toxins often making it responsible for many toxin-mediated diseases, including staphylococcal toxic shock syndrome, foodborne diseases, and scalded skin syndrome.

A major issue associated with S. aureus is its ability to acquire resistance to most antibiotics. Clinical use of methicillin has led to the emergence of methicillin-resistant S. aureus (MRSA) associated with high morbidity and mortality. MRSA strains produce a new altered penicillin-binding protein (PBP 2a or PBP 2’) associated with decreased affinity for penicillins, encoded by the acquired gene mecA carried on a mobile genetic element (MGE) named staphylococcal cassette chromosome mec (SCCmec) that can be acquired and inserted into the chromosomes of susceptible strains. Another resistance determinant has been rarely identified among MRSA, mecC. MRSA isolates are, therefore, resistant to all available penicillins and most of the other beta-lactam drugs, except ceftaroline and ceftobiprole. Vancomycin has historically been the drug of choice, sometimes considered as the last line for the treatment of serious MRSA infections. However, vancomycin is considered less effective than penicillin, and its increased use has been associated with the rise of vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) in some regions.

In the beginning, MRSA was associated only with healthcare settings, the so-called hospital-associated MRSA (HA-MRSA). however, community-acquired MRSA (CA-MRSA) infections have been rising in frequency and now MRSA strains represent a major cause of community-associated infections. CA-MRSA is genetically distinct from HA-MRSA, being resistant to fewer non-beta-lactam antibiotics, carrying a smaller trait of SCCmec, and often producing the Panton-Valentine leukocidin. Moreover, CA-MRSA invading healthcare settings has been also identified as the etiological agent of nosocomial outbreaks. Apart from humans, MRSA colonization and infection have also been reported in animals, for example, in domesticated livestock, companion animals, and wild species. The indiscriminate use of antimicrobial agents in these settings strongly contributed to the spread of MRSA among livestock. Numerous studies have indicated that humans in contact with livestock can be colonized and infected with livestock-associated MRSA (LA-MRSA). Thus, livestock and other animals may become a permanent reservoir for human MRSA infections.

In this Special Issue, we plan to collect original research articles, short communications, or review articles that discuss the pathogenesis of S. aureus infections, and genetic and molecular basis of drug resistance mechanisms in both humans and animals.

Prof. Dr. Giovanni Gherardi
Guest Editor

Manuscript Submission Information

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Keywords

  • S. aureus
  • MRSA
  • pathogenesis
  • antibiotic resistance
  • diagnostic methods

Published Papers (4 papers)

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Research

Article
Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells
Int. J. Mol. Sci. 2021, 22(8), 4015; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084015 - 13 Apr 2021
Viewed by 362
Abstract
Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In [...] Read more.
Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In this study, we confirmed S. aureus to be internalized by HaCaT cells using the ESAT-6-like protein EsxB and amplified within the host over time by escaping host immunity. S. aureus increases the expression of decay-accelerating factor (CD55) on the surfaces of host cells, which inhibits the activation of the complement system. This mechanism makes it possible for S. aureus to survive in host cells. S. aureus, sufficiently amplified within the host, is released through the initiation of cell death. On the other hand, the infected host cells increase their surface expression of UL16 binding protein 1 to inform immune cells that they are infected and try to be eliminated. These host defense systems seem to involve the alteration of tight junctions and the induction of ligand expression to activate immune cells. Taken together, our study elucidates a novel aspect of the mechanisms of infection and immune system evasion for S. aureus. Full article
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Article
Nusbiarylins Inhibit Transcription and Target Virulence Factors in Bacterial Pathogen Staphylococcus aureus
Int. J. Mol. Sci. 2020, 21(16), 5772; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165772 - 11 Aug 2020
Cited by 1 | Viewed by 919
Abstract
The emergence of multidrug resistance in the clinically significant pathogen Staphylococcus aureus is a global health burden, compounded by a diminishing drug development pipeline, and a lack of approved novel antimicrobials. Our previously reported first-in-class bacterial transcription inhibitors “nusbiarylins” presented a promising prospect [...] Read more.
The emergence of multidrug resistance in the clinically significant pathogen Staphylococcus aureus is a global health burden, compounded by a diminishing drug development pipeline, and a lack of approved novel antimicrobials. Our previously reported first-in-class bacterial transcription inhibitors “nusbiarylins” presented a promising prospect towards the discovery of novel antimicrobial agents with a novel mechanism. Here we investigated and characterised the lead nusbiarylin compound, MC4, and several of its chemical derivatives in both methicillin-resistant S. aureus (MRSA) and the S. aureus type strains, demonstrating their capacity for the arrest of growth and cellular respiration, impairment of RNA and intracellular protein levels at subinhibitory concentrations. In some instances, derivatives of MC4 were also shown to attenuate the production of staphylococcal virulence factors in vitro, such as the exoproteins α-toxin and Panton–Valentine Leukocidin (PVL). Trends observed from quantitative PCR assays suggested that nusbiarylins elicited these effects possibly by acting via but not limited to the modulation of global regulatory pathways, such as the agr regulon, which coordinates the expression of S. aureus genes associated with virulence. Our findings encourage the continued development of more potent compounds within this novel family of bacterial transcription inhibitors. Full article
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Article
All d-Lysine Analogues of the Antimicrobial Peptide HPA3NT3-A2 Increased Serum Stability and without Drug Resistance
Int. J. Mol. Sci. 2020, 21(16), 5632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165632 - 06 Aug 2020
Viewed by 555
Abstract
Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and [...] Read more.
Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and mammals. HPA3NT3-A2 ([Ala1,8] HPA3NT3) is an antimicrobial peptide that is an analogue of the HP (2–20) peptide derived from Helicobacter pylori ribosomal protein L1. Although this peptide was shown to have strong antimicrobial activity against drug-resistant bacteria, it also showed lower toxicity against sheep red blood cells (RBCs) and HaCaT cells compared to HPA3NT3. The l-Lys residues of HPA3NT3-A2 was substituted with d-Lys residues (HPA3NT3-A2D; [d-Lys2,5,6,9,10,15] HPA3NT3-A2) to prevent the cleavage of peptide bonds by proteolytic enzymes under physiological conditions. This peptide showed an increased half-life and maintained its antimicrobial activity in the serum against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (pathogen). Furthermore, the antimicrobial activity of HPA3NT3-A2D was not significantly affected in the presence of mono- or divalent ions (Na+, Mg2+, Ca2+). Finally, l- or d-HPA3NT3-A2 peptides exhibited the strongest antimicrobial activity against antibiotic-resistant bacteria and failed to induce resistance in Staphylococcus aureus after 12 passages. Full article
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Article
A Novel Ruthenium Based Coordination Compound Against Pathogenic Bacteria
Int. J. Mol. Sci. 2020, 21(7), 2656; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072656 - 10 Apr 2020
Cited by 2 | Viewed by 1413
Abstract
The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron [...] Read more.
The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239: SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c mice) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected mice were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in mice and subsequently treated with synthesized RU-S4. Full article
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