Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts

Tuchscherr, Lorena; Korpos, Éva; Vyver, Hélène Van de; Findeisen, Clais R.; Kherkheulidze, Salome; Siegmund, Anke; Deinhardt‐Emmer, Stefanie; Bach, Olaf; Rindert, Martin; Mellmann, Alexander; Sunderkötter, Cord; Peters, Georg; Sorokin, Lydia; Löffler, Bettina

doi:10.1016/j.ijmm.2018.05.004

Cited by 17 publications

(15 citation statements)

References 50 publications

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“…Interestingly, this strain had low ability of invasion into the PHSF cells, pointing to the vital role of fnbA and fnbB genes in adhesion to host cells. Similar to our observation, Tuchscherr, Korpos [ 5 ] showed that the lack of human umbilical vein endothelial cells (HUVECs) invasiveness in S. aureus isolates was due to defects in FnBPs. The fnBP genes are commonly detected in S. aureus and different researchers reported variable percentages of the fnbA and fnbB genes.…”

Section: Discussionsupporting

confidence: 91%

“…Patients usually suffer from infected foot ulcers, which increases the complexity of their treatment. About 15% of patients with DM develop foot ulcers that may progress to osteomyelitis and amputation [ 5 ]. These bacterial infections are usually caused by the coagulase-positive Staphylococcus aureus ( S. aureus ) and also the emerging CoNS, including Staphylococcus epidermidis ( S. epidermidis ) and S. haemolyticus [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Pathogenesis of Staphylococcus haemolyticus on primary human skin fibroblast cells

et al. 2020

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Staphylococcus haemolyticus ( S. haemolyticus ) is one of the Coagulase-negative staphylococci (CoNS) that inhabits the skin as a commensal. It is increasingly implicated in opportunistic infections, including diabetic foot ulcer (DFU) infections. In contrast to the abundance of information available for S. aureus and S. epidermidis , little is known about the pathogenicity of S. haemolyticus , despite the increased prevalence of this pathogen in hospitalized patients. We described, for the first time, the pathogenesis of different clinical isolates of S. haemolyticus isolated from DFU on primary human skin fibroblast (PHSF) cells. Virulence-related genes were investigated, adhesion and invasion assays were carried out using Giemsa stain, transmission electron microscopy (TEM), MTT and flowcytometry assays. Our results showed that most S. haemolyticus carried different sets of virulence-related genes. S. haemolyticus adhered to the PHSF cells to variable degrees. TEM showed that the bacteria were engulfed in a zipper-like mechanism into a vacuole inside the cell. Bacterial internalization was confirmed using flowcytometry and achieved high intracellular levels. PHSF cells infected with S.haemolyticus suffered from amarked decrease in viability and increased apoptosis when treated with whole bacterial suspensions or cell-free supernatants but not with heat-treated cells. After co-culture with PBMCs, S. haemolyticus induced high levels of pro-inflammatory cytokines. This study highlights the significant development of S. haemolyticus , which was previously considered a contaminant when detected in cultures of clinical samples. Their high ability to adhere, invade and kill the PHSF cells illustrate the severe damage associated with DFU infections. Abbreviations CoNS, coagulase-negative staphylococci; DFU, diabetic foot ulcer; DM, diabetes mellitus; DMEM, Dulbecco’s Modified Eagle Medium; MTT, 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide; PBMCs,peripheral blood mononuclear cells; PHSF, primary human skin fibroblast; CFU, colony-forming unit.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Pathogenesis of Staphylococcus haemolyticus on primary human skin fibroblast cells

et al. 2020

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“…Survival of S. aureus during stationary phase was unaffected by these acidic conditions, indicating that the reduced growth and survival of S. aureus under high glucose conditions is not due to the presence of acidic metabolites. Contrary to these data, murine footpad infection models revealed that hyperglycemia favors bacterial survival (Tuchscherr et al, 2018). Therefore, other internal and external factors, such as stain lineage and serum components, also affect the growth and survival of strains of S. aureus (Croes et al, 2009;Yin et al, 2017).…”

Section: Discussionmentioning

confidence: 79%

Reduced Growth of Staphylococcus aureus Under High Glucose Conditions Is Associated With Decreased Pentaglycine Expression

et al. 2020

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The high-glucose-induced cytotoxicity in diabetes has been widely recognized. Staphylococcus aureus is the most frequent pathogen isolated from diabetic foot ulcers, but the properties of this bacterium under high glucose conditions remain unclear. S. aureus grew in medium usually forms weak biofilm, and which was significantly increased by addition of glucose. However, extracellular DNA (eDNA), an important component of biofilms, was markedly decreased in presence of 15 mM glucose. The reduced eDNA content was not caused by degradation, because the nuclease activity of biofilm supernatants with glucose was significantly decreased due to the acidic pH of the medium. Under planktonic state, the growth of S. aureus was significantly decreased in the Luria-Bertani (LB) medium supplemented with 25 mM glucose, and the reduced growth of S. aureus by glucose was dose-dependent. Except for glucose, the growth of planktonic S. aureus was also markedly decreased by fructose or sucrose. Amounts of acid metabolites were produced under high glucose conditions, but the survival of planktonic S. aureus was unaffected by these acidic conditions. Cells of S. aureus from the culture medium with glucose had a thinner cell wall and highly resistant to lysostaphin compared with the bacteria cultured in LB medium. mRNA expression of genes encoding pentaglycine bridges, the substrate of lysostaphin, was significantly decreased in S. aureus by glucose. In addition to S. aureus, the growth of Staphylococcus haemolyticus and Staphylococcus epidermidis was also significantly decreased by an excess of glucose, but strains of Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa were unaffected by glucose. In conclusion, the reduced growth of S. aureus under high glucose conditions is due to impairment of the unique cell-wall structure, pentaglycine bridges.

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“…The human osteoblast cell line hFOB 1.19 (ATCC CRL-11372) was cultured according to the manufacturer’s protocol. The invasion assay was performed by flow cytometry (BD Accuri™ C6), as described previously [36], but only raw values were used. The rate of cell death in the hFOB 1.19 cells was determined by measuring the uptake of propidium iodide (PI), as described previously [37].…”

Section: Methodsmentioning

confidence: 99%

Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host

Tuchscherr

Pöllath

Siegmund

et al. 2019

Toxins

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Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses.

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Staphylococcus aureus requires less virulence to establish an infection in diabetic hosts

Cited by 17 publications

References 50 publications

Pathogenesis of Staphylococcus haemolyticus on primary human skin fibroblast cells

Pathogenesis of Staphylococcus haemolyticus on primary human skin fibroblast cells

Reduced Growth of Staphylococcus aureus Under High Glucose Conditions Is Associated With Decreased Pentaglycine Expression

Clinical S. aureus Isolates Vary in Their Virulence to Promote Adaptation to the Host

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