Browsing by Subject "Colonization"

Now showing 1 - 5 of 5
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    Diabetes mellitus promotes the nasal colonization of high virulent Staphylococcus aureus through the regulation of SaeRS two-component system
    (Taylor & Francis, 2023) Wang, Qichen; Nurxat, Nadira; Zhang, Lei; Liu, Yao; Wang, Yanan; Zhang, Lei; Zhao, Na; Dai, Yingxin; Jian, Ying; He, Lei; Wang, Hua; Bae, Taeok; Li, Min; Liu, Qian; Microbiology and Immunology, School of Medicine
    Diabetic foot infections are a common complication of diabetes. Staphylococcus aureus is frequently isolated from diabetic foot infections and commonly colonizes human nares. According to the study, the nasal microbiome analysis revealed that diabetic patients had a significantly altered nasal microbial composition and diversity. Typically, the fasting blood glucose (FBG) level had an impact on the abundance and sequence type (ST) of S. aureus in diabetic patients. We observed that highly virulent S. aureus ST7 strains were more frequently colonized in diabetic patients, especially those with poorly controlled FBG, while ST59 was dominant in healthy individuals. S. aureus ST7 strains were more resistant to human antimicrobial peptides and formed stronger biofilms than ST59 strains. Critically, S. aureus ST7 strains displayed higher virulence compared to ST59 strains in vivo. The dominance of S. aureus ST7 strains in hyperglycemic environment is due to the higher activity of the SaeRS two-component system (TCS). S. aureus ST7 strains outcompeted ST59 both in vitro, and in nasal colonization model in diabetic mice, which was abolished by the deletion of the SaeRS TCS. Our data indicated that highly virulent S. aureus strains preferentially colonize diabetic patients with poorly controlled FBG through SaeRS TCS. Detection of S. aureus colonization and elimination of colonizing S. aureus are critical in the care of diabetic patients with high FBG.
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    Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness
    (MDPI, 2016-11-26) Olivos III, David J.; Mayo, Lindsey D.; Department of Microbiology & Immunology, IU School of Medicine
    Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche. We will also examine p53 gain of function (GOF) roles in stemness. Mutant p53 (mutp53) GOFs that lead to survival, drug resistance and colonization are reviewed in the context of the acquisition of advantageous transformation processes, such as differentiation and dedifferentiation, epithelial-to-mesenchymal transition (EMT) and stem cell senescence and quiescence. Finally, we will conclude with therapeutic strategies that restore wild-type p53 (wtp53) function in cancer and CSCs, including RING finger E3 ligases and CSC maintenance. The mechanisms by which wtp53 and mutp53 influence stemness in non-malignant stem cells and CSCs or tumor-initiating cells (TICs) are poorly understood thus far. Further elucidation of p53's effects on stemness could lead to novel therapeutic strategies in cancer research.
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    Molecular characterization of β-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii
    (BMC, 2017-11-16) Raible, Kevin M.; Sen, Bhaswati; Law, Nancy; Bias, Tiffany E.; Emery, Christopher L.; Ehrlich, Garth D.; Joshi, Suresh G.; Pathology and Laboratory Medicine, School of Medicine
    Background Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Methods In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. Results We determined that all 26 CRAB isolates possessed multiple β-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like β-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010–2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. Conclusions This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period. Electronic supplementary material The online version of this article (10.1186/s12941-017-0248-3) contains supplementary material, which is available to authorized users.
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    The Role of Chlamydia Protein TC0600 in Gastrointestinal Tract Infection
    (2021-12) Alrebdi, Waleed; Nelson, David; Bauer, Margaret; Yang, X. Frank
    Chlamydia is the most frequently reported bacterial sexually transmitted infection in the world. Most urogenital chlamydia infections in men and women are asymptomatic, but these infections can lead to irreparable damage in the reproductive system and other tissues. Apart from the urogenital chlamydial infections, we know that chlamydia infects the gastrointestinal tract (GIT) in humans and can colonize the GIT for extended intervals without eliciting pathology. We are interested in investigating tissue tropism determinants in Chlamydia spp. because these could be targeted to development live-attenuated vaccines. Recently, we generated mutagenized isolates of the mouse pathogen Chlamydia muridarum, a close relative of the human pathogen Chlamydia trachomatis which causes chlamydia. One mutant that we isolated is significantly attenuated in murine gastrointestinal tissues compared to wild type, but retains its pathogenicity in the murine urogenital tract. Using novel genetic techniques, whole-genome sequencing, and complementation using newly developed vector systems we identified a chromosomal factor, tc0600, that we believe mediates the altered tissue tropism phenotype of this mutant in mice. Notably, the Chlamydia trachomatis ortholog of tc0600 has been linked to chlamydial GIT tropism in humans.
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    Virulence adaption to environment promotes the age-dependent nasal colonization of Staphylococcus aureus
    (Taylor & Francis, 2022) Zhao, Na; Cheng, Danhong; Yang, Ziyu; Liu, Yao; Wang, Yanan; Jian, Ying; Wang, Hua; Li, Min; Bae, Taeok; Liu, Qian; Microbiology and Immunology, School of Medicine
    Staphylococcus aureus is an important human commensal bacteria colonizing the human body, especially the nasal cavity. The nasal carriage can be a source of S. aureus bacteremia. However, the bacterial factors contributing to nasal colonization are not completely understood. By analysing S. aureus strains from the nasal cavity of the children, young adults, and seniors, we found that the low activity of the SaeRS two-component system (TCS) is an important determinant for S. aureus to colonize in seniors. The senior group isolates of S. aureus showed a rather distinct sequence type composition as compared with other age group isolates. The senior group isolates showed not only a lower gene carriage of enterotoxins a, c, and q but also lower hemolytic activity against human red blood cells. Of regulators affecting hemolysin production (i.e. agr, saeRS, rot, rsp, and sarS), only the SaeRS TCS showed an age-dependent decrease of activity. The decreased virulence and better colonization ability of the senior group isolates of S. aureus were confirmed in the mouse model. The senior group isolates showed the lowest survival and the best adhesion and colonizing ability. Also, the senior nasal secretions supported S. aureus survival better than the child and young adult nasal secretions. These results indicated that the senior nasal cavity favours colonization of S. aureus with higher adhesion and lower virulence, to which the reduced SaeRS TCS activity contributes. Taken together, our results illustrate an example of bacterial adaptation to the changing host environment.