Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

Oyama, Takuto; Miyazaki, Motonobu; Yoshimura, Michinobu; Takata, Tohru; Ohjimi, Hiroyuki; Jimi, Shiro

doi:10.3390/toxins8070198

Cited by 32 publications

(28 citation statements)

References 49 publications

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“…For the present study, we used an established MRSA strain (ATCC 33591). One hundred and seventy-four clinical samples of MRSA were isolated in Fukuoka University Hospital, one of which (OJ-1) was from an ulcerated wound [ 13 ] and four (T12, T34, T41 and T144) were from blood [ 14 ]. These particular bacterial isolates were selected because of their superior ability to form stable biofilms.…”

Section: Methodsmentioning

confidence: 99%

Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model

Jimi

Miyazaki

Takata

et al. 2017

Journal of Medical Microbiology

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PurposeMeticillin-resistant Staphylococcus aureus (MRSA) biofilm formation in humans is of serious clinical concern. Previous in vitro studies have been performed with biofilms grown only on inorganic substrates; therefore, we investigated the vancomycin (VCM) resistance of MRSA biofilms grown on skin tissue.MethodologyWe established a novel tissue substrate model, namely MRSA grown on segments of mouse skin tissue (dermal chips, DCs), and compared its resistance capacity against VCM with that of MRSA biofilms grown on plastic chips (PCs).Results/Key findingsFor one MRSA isolate, we found that the VCM MIC was identical (1.56 µg ml−1) for planktonic cultures and for biofilms-formed on PCs (PC-BF), although the minimum bactericidal concentration (MBC) increased to 6.25 µg ml−1 in PC-BF. On the contrary, the MIC and MBC for biofilms formed on DCs (DC-BF) significantly increased (25 and 50 µg ml−1, respectively). Furthermore, the minimum biofilm-eradicating concentration was higher for DC-BF (100 µg ml−1) than for PC-BF (25 µg ml−1). Using six MRSA strains, we found that in PC-BF, the c.f.u. number decreased with increasing VCM concentration, whereas in DC-BF, it greatly increased until the MIC was reached, accompanied by the formation of large colonies, thicker bacterial walls and the presence of many mitotic cells.ConclusionOur results indicate that the VCM resistance of MRSA was greater in DC-BF. We conclude that DCs may provide a specific environment for MRSA that enhances bacterial growth under cytotoxic VCM concentrations, and might be useful for the study of skin wound infections and the effects of antimicrobial drugs.

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Section: Methodsmentioning

confidence: 99%

Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model

Jimi

Miyazaki

Takata

et al. 2017

Journal of Medical Microbiology

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“…MSCRAMMs act as adhesin receptors to facilitate the attachment and specific binding to the extracellular matrix. The isolates also harboured intercellular adhesion proteins (icaA, icaB, icaC, icaD, icaR) associated with attachment, proliferation and differentiation of micro-colonies into unique biofilm structures protecting them from the host defences such as antibodies or phagocytosis, making them extremely difficult to eradicate [54,55]. The association of dominant clonal lineages and biofilm formation has been reported in various studies on MRSA [56][57][58][59].…”

Section: Discussionmentioning

confidence: 94%

Genome Mining and Comparative Pathogenomic Analysis of An Endemic Methicillin-Resistant Staphylococcus Aureus (MRSA) Clone, ST612-CC8-t1257-SCCmec_IVd(2B), Isolated in South Africa

et al. 2019

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This study undertook genome mining and comparative genomics to gain genetic insights into the dominance of the methicillin-resistant Staphylococcus aureus (MRSA) endemic clone ST612-CC8-t1257-SCCmec_IVd(2B), obtained from the poultry food chain in South Africa. Functional annotation of the genome revealed a vast array of similar central metabolic, cellular and biochemical networks within the endemic clone crucial for its survival in the microbial community. In-silico analysis of the clone revealed the possession of uniform defense systems, restriction-modification system (type I and IV), accessory gene regulator (type I), arginine catabolic mobile element (type II), and type 1 clustered, regularly interspaced, short palindromic repeat (CRISPR)Cas array (N = 7 ± 1), which offer protection against exogenous attacks. The estimated pathogenic potential predicted a higher probability (average Pscore ≈ 0.927) of the clone being pathogenic to its host. The clone carried a battery of putative virulence determinants whose expression are critical for establishing infection. However, there was a slight difference in their possession of adherence factors (biofilm operon system) and toxins (hemolysins and enterotoxins). Further analysis revealed a conserved environmental tolerance and persistence mechanisms related to stress (oxidative and osmotic), heat shock, sporulation, bacteriocins, and detoxification, which enable it to withstand lethal threats and contribute to its success in diverse ecological niches. Phylogenomic analysis with close sister lineages revealed that the clone was closely related to the MRSA isolate SHV713 from Australia. The results of this bioinformatic analysis provide valuable insights into the biology of this endemic clone.

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“…Some studies indicate that about 2.1% of the population are colonized with MRSA, which was lower in orthopedic patients (0.9%) and higher in neurologic patients (3.7%) [ 17 ]. Notably, MRSA forms biofilms not only on indwelling foreign body infections, but also in bacteremia, endocarditis, soft-tissue infections, and osteomyelitis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we successfully established a model of MRSA-BF infection in rats by CTX-induced immunosuppression. The model was based on previous rat models for bacterial BF and invasive MRSA [ 6 , 7 , 14 , 18 – 21 ]. To confirm that BF infection was consistent with that observed in humans, we assessed overall appearance, survival, WBC counts, and SEM images.…”

Section: Discussionmentioning

confidence: 99%

Generation of Methicillin-Resistant Staphylococcus Aureus Biofilm Infection in an Immunosuppressed Rat Model

Liu

Chen

et al. 2017

Med Sci Monit

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BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen responsible for many related infections, and immunosuppressed individuals are more susceptible. Its pathogenicity is associated with its virulence factors, resistance to antibiotics, and ability to form biofilm (BF). MRSA-BF infections in immunosuppressed patients pose great difficulties to clinical treatment.Material/MethodsThe study aimed to establish a model of MRSA-BF infection in rats with cyclophosphamide (CTX)-induced immunosuppression. For this, rats were administered CTX on days 1 and 4. White blood cells (WBC) were counted, then rats were inoculated with a clinical MRSA 17546 (t037) on day 5. Rats were sacrificed on days 6–10 and tissue samples were examined by scanning electron microscopy.ResultsUsing the dose of CTX: 150 (mg/kg) + 100 (mg/kg) is better than the other 2 programs as the survival rates of the immunocompromised rats were higher than in the other 2 immunosuppressive groups. The survival rate was not different between rats in the clean environment and in the SPF environment. However, the survival rate was affected by the sample acquisitions. Importantly, WBC counts started to decline on day 4, and then started to rise on day 9. Moreover, MRSA-BFs were formed earlier in immunosuppressed rats compared to the normal rats, as shown by scanning electron microscopy.ConclusionsThe study successfully established an immunosuppressed rat model of MRSA-BF infection, which provides methodological and data support for establishment of such animal models and is useful reference for related research. Our results may help further investigation of MRSA-BF infection.

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Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

Cited by 32 publications

References 49 publications

Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model

Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model

Genome Mining and Comparative Pathogenomic Analysis of An Endemic Methicillin-Resistant Staphylococcus Aureus (MRSA) Clone, ST612-CC8-t1257-SCCmec_IVd(2B), Isolated in South Africa

Generation of Methicillin-Resistant Staphylococcus Aureus Biofilm Infection in an Immunosuppressed Rat Model

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