Staphylococcal Infections (Host and Pathogenic Factors)

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 57575

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Dear Colleagues,

Although 30% of the healthy human population is colonized with various Staphylococcus spp., some staphylococcal strains, referred to as opportunistic pathogens, can cause minor to life-threatening diseases. The pathogenicity of these bacteria depends on their virulence factors and the robustness of the regulatory networks expressing these virulence factors. Virulence factors of pathogenic Staphylococcus spp. consist of numerous toxins, enterotoxins (some of which act as superantigens), enzymes, and proteins (cytoplasmic, extracellular, and surface) that are regulated by two-component (TC) and quorum-sensing (QS) regulatory networks. For example, based on their homology with quorum-sensing molecules/components, one Staphylococcus aureus species can alter the toxin/surface protein production of another S. aureus species either synergistically or antagonistically. To invade this niche, some other Staphylococcus species, such as Staphylococcus simulans, produce a potent endopeptidase called lysostaphin, which can lyse and eradicate the pathogenic S. aureus. Some other Staphylococcus species produce autolysins and cationic peptides to win the intra- and inter-species competition. The outcome of this microbial invasion depends not only on pathogenic factors but also on the host’s internal and external defense mechanisms, including a healthy skin microbiome. A healthy skin microbiome population consisting of Staphylococcus epidermidis can prevent colonization by other major pathogens. As normal host microflora, these commensals establish a complex relationship with the host as well as the surrounding microbial communities. This Special Issue of Microorganisms is focused on studies and recent advancements in our understanding of staphylococcal virulence mechanisms that enable Staphylococcus spp. either to successfully establish themselves as a colonizer or to overcome the host’s defense system to cause infection.

Dr. Rajan P. Adhikari
Guest Editor

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Keywords

  • S. aureus
  • S. epidermidis
  • Staphylococcus spp.
  • pore-forming toxins (hemolysins and leukotoxins)
  • quorum sensing (QS) and two component (TC) systems
  • colonization
  • biofilm formation
  • surface proteins
  • enterotoxins (superantigens)

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Published Papers (15 papers)

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Editorial

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8 pages, 184 KiB  
Editorial
Staphylococcal Infections: Host and Pathogenic Factors
by Rajan P. Adhikari
Microorganisms 2021, 9(5), 1080; https://doi.org/10.3390/microorganisms9051080 - 18 May 2021
Cited by 6 | Viewed by 2686
Abstract
In 1880, the Scottish surgeon Sir Alexander Ogston first described staphylococci in pus from a surgical abscess in a knee joint: “The masses looked like bunches of grapes” [...] Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))

Research

Jump to: Editorial, Review

12 pages, 485 KiB  
Article
Cell Membrane Adaptations Mediate β-Lactam-Induced Resensitization of Daptomycin-Resistant (DAP-R) Staphylococcus aureus In Vitro
by Nagendra N. Mishra, Arnold S. Bayer, Sarah L. Baines, Ashleigh S. Hayes, Benjamin P. Howden, Christian K. Lapitan, Cassandra Lew and Warren E. Rose
Microorganisms 2021, 9(5), 1028; https://doi.org/10.3390/microorganisms9051028 - 11 May 2021
Cited by 6 | Viewed by 2933
Abstract
The reversal of daptomycin resistance in MRSA to a daptomycin-susceptible phenotype following prolonged passage in selected β-lactams occurs coincident with the accumulation of multiple point mutations in the mprF gene. MprF regulates surface charge by modulating the content and translocation of the positively [...] Read more.
The reversal of daptomycin resistance in MRSA to a daptomycin-susceptible phenotype following prolonged passage in selected β-lactams occurs coincident with the accumulation of multiple point mutations in the mprF gene. MprF regulates surface charge by modulating the content and translocation of the positively charged cell membrane phospholipid, lysyl-phosphatidylglycerol (LPG). The precise cell membrane adaptations accompanying such β-lactam-induced mprF perturbations are unknown. This study examined key cell membrane metrics relevant to antimicrobial resistance among three daptomycin-resistant MRSA clinical strains, which became daptomycin-susceptible following prolonged exposure to cloxacillin (‘daptomycin-resensitized’). The causal role of such secondary mprF mutations in mediating daptomycin resensitization was confirmed through allelic exchange strategies. The daptomycin-resensitized strains derived either post-cloxacillin passage or via allelic exchange (vs. their respective daptomycin-resistant strains) showed the following cell membrane changes: (i) enhanced BODIPY-DAP binding; (ii) significant reductions in LPG content, accompanied by significant increases in phosphatidylglycerol content (p < 0.05); (iii) no significant changes in positive cell surface charge; (iv) decreased cell membrane fluidity (p < 0.05); (v) enhanced carotenoid content (p < 0.05); and (vi) lower branched chain fatty acid profiles (antiso- vs. iso-), resulting in increases in saturated fatty acid composition (p < 0.05). Overall, the cell membrane characteristics of the daptomycin-resensitized strains resembled those of parental daptomycin-susceptible strains. Daptomycin resensitization with selected β-lactams results in both definable genetic changes (i.e., mprF mutations) and a number of key cell membrane phenotype modifications, which likely facilitate daptomycin activity. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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10 pages, 892 KiB  
Communication
Mild Lactic Acid Stress Causes Strain-Dependent Reduction in SEC Protein Levels
by Danai Etter, Céline Jenni, Taurai Tasara and Sophia Johler
Microorganisms 2021, 9(5), 1014; https://doi.org/10.3390/microorganisms9051014 - 8 May 2021
Cited by 4 | Viewed by 2394
Abstract
Staphylococcal enterotoxin C (SEC) is a major cause of staphylococcal food poisoning in humans and plays a role in bovine mastitis. Staphylococcus aureus (S. aureus) benefits from a competitive growth advantage under stress conditions encountered in foods such as a low [...] Read more.
Staphylococcal enterotoxin C (SEC) is a major cause of staphylococcal food poisoning in humans and plays a role in bovine mastitis. Staphylococcus aureus (S. aureus) benefits from a competitive growth advantage under stress conditions encountered in foods such as a low pH. Therefore, understanding the role of stressors such as lactic acid on SEC production is of pivotal relevance to food safety. However, stress-dependent cues and their effects on enterotoxin expression are still poorly understood. In this study, we used human and animal strains harboring different SEC variants in order to evaluate the influence of mild lactic acid stress (pH 6.0) on SEC expression both on transcriptional and translational level. Although only a modest decrease in sec mRNA levels was observed under lactic acid stress, protein levels showed a significant decrease in SEC levels for some strains. These findings indicate that post-transcriptional modifications can act in SEC expression under lactic acid stress. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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20 pages, 2273 KiB  
Article
Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization
by Liliane Maria Fernandes de Oliveira, Marina Steindorff, Murthy N. Darisipudi, Daniel M. Mrochen, Patricia Trübe, Barbara M. Bröker, Mark Brönstrup, Werner Tegge and Silva Holtfreter
Microorganisms 2021, 9(3), 631; https://doi.org/10.3390/microorganisms9030631 - 18 Mar 2021
Cited by 8 | Viewed by 3447
Abstract
Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert [...] Read more.
Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit S. aureus adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay. The assay quantified DAPI-stained nuclei of the host cell; attached bacteria were stained with an anti-teichoic acid antibody. The most promising candidate, aurintricarboxylic acid (ATA), was evaluated in a novel persistent S. aureus nasal colonization model using a mouse-adapted S. aureus strain. Colonized mice were treated intranasally over 7 days with ATA using a wide dose range (0.5–10%). Mupirocin completely eliminated the bacteria from the nose within three days of treatment. In contrast, even high concentrations of ATA failed to eradicate the bacteria. To conclude, our imaging-based assay and the persistent colonization model provide excellent tools to identify and validate new drug candidates against S. aureus nasal colonization. However, our first tested candidate ATA failed to induce S. aureus decolonization. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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16 pages, 2901 KiB  
Article
Impact of the Histidine-Containing Phosphocarrier Protein HPr on Carbon Metabolism and Virulence in Staphylococcus aureus
by Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff and Rosmarie Gaupp
Microorganisms 2021, 9(3), 466; https://doi.org/10.3390/microorganisms9030466 - 24 Feb 2021
Cited by 12 | Viewed by 2642
Abstract
Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram-positive bacteria, catabolite control protein A (CcpA) and the histidine-containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. [...] Read more.
Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram-positive bacteria, catabolite control protein A (CcpA) and the histidine-containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading frame or harbor a ptsH variant carrying a thymidine to guanosine mutation at position 136, and the effects of these mutations on growth and metabolism were assessed. Inactivation of ptsH altered bacterial physiology and decreased the ability of S. aureus to form a biofilm and cause infections in mice. These data demonstrate that HPr affects central metabolism and virulence in S. aureus independent of its influence on CcpA regulation. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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23 pages, 5334 KiB  
Article
A Murine Skin Infection Model Capable of Differentiating the Dermatopathology of Community-Associated MRSA Strain USA300 from Other MRSA Strains
by Jack Zhang, John Conly, JoAnn McClure, Kaiyu Wu, Bjӧrn Petri, Duane Barber, Sameer Elsayed, Glen Armstrong and Kunyan Zhang
Microorganisms 2021, 9(2), 287; https://doi.org/10.3390/microorganisms9020287 - 30 Jan 2021
Cited by 2 | Viewed by 5337
Abstract
USA300 is a predominant and highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain that is a leading cause of skin and soft tissue infections. We established a murine intradermal infection model capable of demonstrating dermatopathological differences between USA300 and other MRSA strains. In [...] Read more.
USA300 is a predominant and highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain that is a leading cause of skin and soft tissue infections. We established a murine intradermal infection model capable of demonstrating dermatopathological differences between USA300 and other MRSA strains. In this model, USA300 induced dermonecrosis, uniformly presenting as extensive open lesions with a histologically documented profound inflammatory cell infiltrate extending below the subcutis. In contrast, USA400 and a colonizing control strain M92 caused only localized non-ulcerated skin infections associated with a mild focal inflammatory infiltrate. It was also determined that the dermonecrosis induced by USA300 was associated with significantly increased neutrophil recruitment, inhibition of an antibacterial response, and increased production of cytokines/chemokines associated with disease severity. These results suggest that induction of severe skin lesions by USA300 is related to over-activation of neutrophils, inhibition of host antibacterial responses, and selective alteration of host cytokine/chemokine profiles. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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14 pages, 795 KiB  
Article
Methicillin-Resistant Staphylococcus epidermidis Lineages in the Nasal and Skin Microbiota of Patients Planned for Arthroplasty Surgery
by Emeli Månsson, Staffan Tevell, Åsa Nilsdotter-Augustinsson, Thor Bech Johannesen, Martin Sundqvist, Marc Stegger and Bo Söderquist
Microorganisms 2021, 9(2), 265; https://doi.org/10.3390/microorganisms9020265 - 28 Jan 2021
Cited by 6 | Viewed by 3008
Abstract
Staphylococcus epidermidis, ubiquitous in the human nasal and skin microbiota, is a common causative microorganism in prosthetic joint infections (PJIs). A high proportion of PJI isolates have been shown to harbor genetic traits associated with resistance to/tolerance of agents used for antimicrobial [...] Read more.
Staphylococcus epidermidis, ubiquitous in the human nasal and skin microbiota, is a common causative microorganism in prosthetic joint infections (PJIs). A high proportion of PJI isolates have been shown to harbor genetic traits associated with resistance to/tolerance of agents used for antimicrobial prophylaxis in joint arthroplasties. These traits were found within multidrug-resistant S. epidermidis (MDRSE) lineages of multiple genetic backgrounds. In this study, the aim was to study whether MDRSE lineages previously associated with PJIs are present in the nasal and skin microbiota of patients planned for arthroplasty surgery but before hospitalization. We cultured samples from nares, inguinal creases, and skin over the hip or knee (dependent on the planned procedure) taken two weeks (median) prior to admittance to the hospital for total joint arthroplasty from 66 patients on agar plates selecting for methicillin resistance. S. epidermidis colonies were identified and tested for the presence of mecA. Methicillin-resistant S. epidermidis (MRSE) were characterized by Illumina-based whole-genome sequencing. Using this method, we found that 30/66 (45%) of patients were colonized with MRSE at 1–3 body sites. A subset of patients, 10/66 (15%), were colonized with MDRSE lineages associated with PJIs. The qacA gene was identified in MRSE isolates from 19/30 (63%) of MRSE colonized patients, whereas genes associated with aminoglycoside resistance were less common, found in 11/30 (37%). We found that MDRSE lineages previously associated with PJIs were present in a subset of patients’ pre-admission microbiota, plausibly in low relative abundance, and may be selected for by the current prophylaxis regimen comprising whole-body cleansing with chlorhexidine-gluconate containing soap. To further lower the rate of S. epidermidis PJIs, the current prophylaxis may need to be modified, but it is important for possible perioperative MDRSE transmission events and specific risk factors for MDRSE PJIs to be investigated before reevaluating antimicrobial prophylaxis. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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13 pages, 1652 KiB  
Article
Performance of a Four-Antigen Staphylococcus aureus Vaccine in Preclinical Models of Invasive S. aureus Disease
by Ingrid L. Scully, Yekaterina Timofeyeva, Arthur Illenberger, Peimin Lu, Paul A. Liberator, Kathrin U. Jansen and Annaliesa S. Anderson
Microorganisms 2021, 9(1), 177; https://doi.org/10.3390/microorganisms9010177 - 15 Jan 2021
Cited by 19 | Viewed by 5133
Abstract
A Staphylococcus aureus four-antigen vaccine (SA4Ag) was designed for the prevention of invasive disease in surgical patients. The vaccine is composed of capsular polysaccharide type 5 and type 8 CRM197 conjugates, a clumping factor A mutant (Y338A-ClfA) and manganese transporter subunit C [...] Read more.
A Staphylococcus aureus four-antigen vaccine (SA4Ag) was designed for the prevention of invasive disease in surgical patients. The vaccine is composed of capsular polysaccharide type 5 and type 8 CRM197 conjugates, a clumping factor A mutant (Y338A-ClfA) and manganese transporter subunit C (MntC). S. aureus pathogenicity is characterized by an ability to rapidly adapt to the host environment during infection, which can progress from a local infection to sepsis and invasion of distant organs. To test the protective capacity of the SA4Ag vaccine against progressive disease stages of an invasive S. aureus infection, a deep tissue infection mouse model, a bacteremia mouse model, a pyelonephritis model, and a rat model of infectious endocarditis were utilized. SA4Ag vaccination significantly reduced the bacterial burden in deep tissue infection, in bacteremia, and in the pyelonephritis model. Complete prevention of infection was demonstrated in a clinically relevant endocarditis model. Unfortunately, these positive preclinical findings with SA4Ag did not prove the clinical utility of SA4Ag in the prevention of surgery-associated invasive S. aureus infection. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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7 pages, 245 KiB  
Communication
Molecular Characterization of Staphylococcus aureus Isolated from Chronic Infected Wounds in Rural Ghana
by Manuel Wolters, Hagen Frickmann, Martin Christner, Anna Both, Holger Rohde, Kwabena Oppong, Charity Wiafe Akenten, Jürgen May and Denise Dekker
Microorganisms 2020, 8(12), 2052; https://doi.org/10.3390/microorganisms8122052 - 21 Dec 2020
Cited by 11 | Viewed by 3297
Abstract
Background: Globally, Staphylococcus aureus is an important bacterial pathogen causing a wide range of community and hospital acquired infections. In Ghana, resistance of S. aureus to locally available antibiotics is increasing but the molecular basis of resistance and the population structure of S. [...] Read more.
Background: Globally, Staphylococcus aureus is an important bacterial pathogen causing a wide range of community and hospital acquired infections. In Ghana, resistance of S. aureus to locally available antibiotics is increasing but the molecular basis of resistance and the population structure of S. aureus in particular in chronic wounds are poorly described. However, this information is essential to understand the underlying mechanisms of resistance and spread of resistant clones. We therefore subjected 28 S. aureus isolates from chronic infected wounds in a rural area of Ghana to whole genome sequencing. Results: Overall, resistance of S. aureus to locally available antibiotics was high and 29% were Methicillin resistant Staphylococcus aureus (MRSA). The most abundant sequence type was ST88 (29%, 8/28) followed by ST152 (18%, 5/28). All ST88 carried the mecA gene, which was associated with this sequence type only. Chloramphenicol resistance gene fexB was exclusively associated with the methicillin-resistant ST88 strains. Panton-Valentine leukocidin (PVL) carriage was associated with ST121 and ST152. Other detected mechanisms of resistance included dfrG, conferring resistance to trimethoprim. Conclusions: This study provides valuable information for understanding the population structure and resistance mechanisms of S. aureus isolated from chronic wound infections in rural Ghana. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
20 pages, 3537 KiB  
Article
Impact of Staphylococcus aureus Small Colony Variants on Human Lung Epithelial Cells with Subsequent Influenza Virus Infection
by Janine J. Wilden, Eike R. Hrincius, Silke Niemann, Yvonne Boergeling, Bettina Löffler, Stephan Ludwig and Christina Ehrhardt
Microorganisms 2020, 8(12), 1998; https://doi.org/10.3390/microorganisms8121998 - 15 Dec 2020
Cited by 2 | Viewed by 2991
Abstract
Human beings are exposed to microorganisms every day. Among those, diverse commensals and potential pathogens including Staphylococcus aureus (S. aureus) compose a significant part of the respiratory tract microbiota. Remarkably, bacterial colonization is supposed to affect the outcome of viral respiratory [...] Read more.
Human beings are exposed to microorganisms every day. Among those, diverse commensals and potential pathogens including Staphylococcus aureus (S. aureus) compose a significant part of the respiratory tract microbiota. Remarkably, bacterial colonization is supposed to affect the outcome of viral respiratory tract infections, including those caused by influenza viruses (IV). Since 30% of the world’s population is already colonized with S. aureus that can develop metabolically inactive dormant phenotypes and seasonal IV circulate every year, super-infections are likely to occur. Although IV and S. aureus super-infections are widely described in the literature, the interactions of these pathogens with each other and the host cell are only scarcely understood. Especially, the effect of quasi-dormant bacterial subpopulations on IV infections is barely investigated. In the present study, we aimed to investigate the impact of S. aureus small colony variants on the cell intrinsic immune response during a subsequent IV infection in vitro. In fact, we observed a significant impact on the regulation of pro-inflammatory factors, contributing to a synergistic effect on cell intrinsic innate immune response and induction of harmful cell death. Interestingly, the cytopathic effect, which was observed in presence of both pathogens, was not due to an increased pathogen load. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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24 pages, 5495 KiB  
Article
Role of SrtA in Pathogenicity of Staphylococcus lugdunensis
by Muzaffar Hussain, Christian Kohler and Karsten Becker
Microorganisms 2020, 8(12), 1975; https://doi.org/10.3390/microorganisms8121975 - 11 Dec 2020
Cited by 10 | Viewed by 3031
Abstract
Among coagulase-negative staphylococci (CoNS), Staphylococcus lugdunensis has a special position as causative agent of aggressive courses of infectious endocarditis (IE) more reminiscent of IEs caused by Staphylococcus aureus than those by CoNS. To initiate colonization and invasion, bacterial cell surface proteins are required; [...] Read more.
Among coagulase-negative staphylococci (CoNS), Staphylococcus lugdunensis has a special position as causative agent of aggressive courses of infectious endocarditis (IE) more reminiscent of IEs caused by Staphylococcus aureus than those by CoNS. To initiate colonization and invasion, bacterial cell surface proteins are required; however, only little is known about adhesion of S. lugdunensis to biotic surfaces. Cell surface proteins containing the LPXTG anchor motif are covalently attached to the cell wall by sortases. Here, we report the functionality of Staphylococcus lugdunensis sortase A (SrtA) to link LPXTG substrates to the cell wall. To determine the role of SrtA dependent surface proteins in biofilm formation and binding eukaryotic cells, we generated SrtA-deficient mutants (ΔsrtA). These mutants formed a smaller amount of biofilm and bound less to immobilized fibronectin, fibrinogen, and vitronectin. Furthermore, SrtA absence affected the gene expression of two different adhesins on transcription level. Surprisingly, we found no decreased adherence and invasion in human cell lines, probably caused by the upregulation of further adhesins in ΔsrtA mutant strains. In conclusion, the functionality of S. lugdunensis SrtA in anchoring LPXTG substrates to the cell wall let us define it as the pathogen’s housekeeping sortase. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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15 pages, 5394 KiB  
Article
Combined Effect of Naturally-Derived Biofilm Inhibitors and Differentiated HL-60 Cells in the Prevention of Staphylococcus aureus Biofilm Formation
by Inés Reigada, Clara Guarch-Pérez, Jayendra Z. Patel, Martijn Riool, Kirsi Savijoki, Jari Yli-Kauhaluoma, Sebastian A. J. Zaat and Adyary Fallarero
Microorganisms 2020, 8(11), 1757; https://doi.org/10.3390/microorganisms8111757 - 9 Nov 2020
Cited by 8 | Viewed by 3188
Abstract
Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, with 80% of these infections being caused by a bacterial biofilm. The insertion of a foreign material usually elicits inflammation, which can result [...] Read more.
Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, with 80% of these infections being caused by a bacterial biofilm. The insertion of a foreign material usually elicits inflammation, which can result in hampered antimicrobial capacity of the host immunity due to the effort of immune cells being directed to degrade the material. The ineffective clearance by immune cells is a perfect opportunity for bacteria to attach and form a biofilm. In this study, we analyzed the antibiofilm capacity of three naturally derived biofilm inhibitors when combined with immune cells in order to assess their applicability in implantable titanium devices and low-density polyethylene (LDPE) endotracheal tubes. To this end, we used a system based on the coculture of HL-60 cells differentiated into polymorphonuclear leukocytes (PMNs) and Staphylococcus aureus (laboratory and clinical strains) on titanium, as well as LDPE surfaces. Out of the three inhibitors, the one coded DHA1 showed the highest potential to be incorporated into implantable devices, as it displayed a combined activity with the immune cells, preventing bacterial attachment on the titanium and LDPE. The other two inhibitors seemed to also be good candidates for incorporation into LDPE endotracheal tubes. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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12 pages, 2295 KiB  
Article
The Effects of Silver Sulfadiazine on Methicillin-Resistant Staphylococcus aureus Biofilms
by Yutaka Ueda, Motoyasu Miyazaki, Kota Mashima, Satoshi Takagi, Shuuji Hara, Hidetoshi Kamimura and Shiro Jimi
Microorganisms 2020, 8(10), 1551; https://doi.org/10.3390/microorganisms8101551 - 8 Oct 2020
Cited by 22 | Viewed by 4531
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA), the most commonly detected drug-resistant microbe in hospitals, adheres to substrates and forms biofilms that are resistant to immunological responses and antimicrobial drugs. Currently, there is a need to develop alternative approaches for treating infections caused by biofilms to [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA), the most commonly detected drug-resistant microbe in hospitals, adheres to substrates and forms biofilms that are resistant to immunological responses and antimicrobial drugs. Currently, there is a need to develop alternative approaches for treating infections caused by biofilms to prevent delays in wound healing. Silver has long been used as a disinfectant, which is non-specific and has relatively low cytotoxicity. Silver sulfadiazine (SSD) is a chemical complex clinically used for the prevention of wound infections after injury. However, its effects on biofilms are still unclear. In this study, we aimed to analyze the mechanisms underlying SSD action on biofilms formed by MRSA. The antibacterial effects of SSD were a result of silver ions and not sulfadiazine. Ionized silver from SSD in culture media was lower than that from silver nitrate; however, SSD, rather than silver nitrate, eradicated mature biofilms by bacterial killing. In SSD, sulfadiazine selectively bound to biofilms, and silver ions were then liberated. Consequently, the addition of an ion-chelator reduced the bactericidal effects of SSD on biofilms. These results indicate that SSD is an effective compound for the eradication of biofilms; thus, SSD should be used for the removal of biofilms formed on wounds. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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Review

Jump to: Editorial, Research

14 pages, 1299 KiB  
Review
No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus
by Vishal Gor, Ryosuke L. Ohniwa and Kazuya Morikawa
Microorganisms 2021, 9(2), 244; https://doi.org/10.3390/microorganisms9020244 - 25 Jan 2021
Cited by 5 | Viewed by 4631
Abstract
Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy [...] Read more.
Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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20 pages, 1803 KiB  
Review
Human mecC-Carrying MRSA: Clinical Implications and Risk Factors
by Carmen Lozano, Rosa Fernández-Fernández, Laura Ruiz-Ripa, Paula Gómez, Myriam Zarazaga and Carmen Torres
Microorganisms 2020, 8(10), 1615; https://doi.org/10.3390/microorganisms8101615 - 20 Oct 2020
Cited by 40 | Viewed by 6708
Abstract
A new methicillin resistance gene, named mecC, was first described in 2011 in both humans and animals. Since then, this gene has been detected in different production and free-living animals and as an agent causing infections in some humans. The possible impact [...] Read more.
A new methicillin resistance gene, named mecC, was first described in 2011 in both humans and animals. Since then, this gene has been detected in different production and free-living animals and as an agent causing infections in some humans. The possible impact that these isolates can have in clinical settings remains unknown. The current available information about mecC-carrying methicillin resistant S. aureus (MRSA) isolates obtained from human samples was analyzed in order to establish its possible clinical implications as well as to determine the infection types associated with this resistance mechanism, the characteristics of these mecC-carrying isolates, their possible relation with animals and the presence of other risk factors. Until now, most human mecC-MRSA infections have been reported in Europe and mecC-MRSA isolates have been identified belonging to a small number of clonal complexes. Although the prevalence of mecC-MRSA human infections is very low and isolates usually contain few resistance (except for beta-lactams) and virulence genes, first isolates harboring important virulence genes or that are resistant to non-beta lactams have already been described. Moreover, severe and even fatal human infection cases have been detected. mecC-carrying MRSA should be taken into consideration in hospital, veterinary and food safety laboratories and in prevention strategies in order to avoid possible emerging health problems. Full article
(This article belongs to the Special Issue Staphylococcal Infections (Host and Pathogenic Factors))
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