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Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen.

ABSTRACT: Staphylococcus pettenkoferi is a coagulase-negative Staphylococcus identified in 2002 that has been implicated in human diseases as an opportunistic pathogenic bacterium. Its multiresistant character is becoming a major health problem, yet the pathogenicity of S. pettenkoferi is poorly characterized. In this study, the pathogenicity of a S. pettenkoferi clinical isolate from diabetic foot osteomyelitis was compared with a Staphylococcus aureus strain in various in vitro and in vivo experiments. Growth kinetics were compared against S. aureus, and bacteria survival was assessed in the RAW 264.7 murine macrophage cell line, the THP-1 human leukemia monocytic cell line, and the HaCaT human keratinocyte cell line. Ex vivo analysis was performed in whole blood survival assays and in vivo assays via the infection model of zebrafish embryos. Moreover, whole-genome analysis was performed. Our results show that S. pettenkoferi was able to survive in human blood, human keratinocytes, murine macrophages, and human macrophages. S. pettenkoferi demonstrated its virulence by causing substantial embryo mortality in the zebrafish model. Genomic analysis revealed virulence factors such as biofilm-encoding genes (e.g., icaABCD; rsbUVW) and regulator-encoding genes (e.g., agr, mgrA, sarA, saeS) well characterized in S. aureus. This study thus advances the knowledge of this under-investigated pathogen and validates the zebrafish infection model for this bacterium.

SUBMITTER: Ahmad-Mansour N

PROVIDER: S-EPMC8704685 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Coagulase Negative Staphylococci (CoNS) are becoming increasingly recognized as an important cause of human and animal infections. Notwithstanding their clinical relevance, annotation of genes potentially involved in pathogenicity and/or antibiotic resistance in the CoNS species Staphylococcus arlettae (SAR) is currently very limited. In the current work we describe the genome of a novel methicillin resistant isolate of SAR, which we named Bari, and present a comprehensive analysis of predicted antibiotic resistance profiles and virulence determinants for all the 22 currently available SAR genomes. By comparing predicted antibiotic resistance and virulence-associated genes with those obtained from a manual selection of 148 bacterial strains belonging to 14 different species of staphylococci and to two "outgroup" species, Bacillus subtilis (BS) and Macrococcus caseoliticus (MC), we derived some interesting observations concerning the types and number of antibiotic resistance-related and virulence-like genes in SAR. Interestingly, almost 50% of the putative antibiotic resistance determinants identified in this work, which include the clinically relevant mec, van, and cls genes, were shared among all the SAR strains herein considered (Bari included). Moreover, comparison of predicted antibiotic resistance profiles suggest that SAR is closely related to well-known pathogenic Staphylococcus species, such as Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE). A similar analysis of predicted virulence factors, revealed that several genes associated with pathogenesis (including, for example, ica, nuc, and ssp), which are commonly found in the genomes of pathogenic staphylococci such as Staphylococcus haemolyticus (SH) and Staphylococcus saprophyticus (SS), are observed also in the SAR strains for which a genomic sequence is available. All in all, we believe that the analyses presented in the current study, by providing a consistent and comprehensive annotation of virulence and antibiotic resistance-related genes in SAR, can constitute a valuable resource for the study of molecular mechanisms of opportunistic pathogenicity in this species.

Project description:Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence.

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Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen.

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