scholarly journals Bacterial carriage of genes encoding fibronectin-binding proteins is associated with long-term persistence of Staphylococcus aureus in the nasal and gut microbiota of infants

2021 ◽  
Author(s):  
Forough L. Nowrouzian ◽  
Annika Ljung ◽  
Bill Hesselmar ◽  
Staffan Nilsson ◽  
Ingegerd Adlerberth ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gut Microbiota ◽  
Virulence Factors ◽  
Current Knowledge ◽  
Nasal Carriage ◽  
Pathogenic Potential ◽  
Gut Colonization ◽  
Genes Encoding ◽  
Fibronectin Binding

Staphylococcus aureus can colonize both the anterior nares and the gastrointestinal tract. However, colonization at these sites in the same individuals has not been studied, and the traits that facilitate colonization and persistence at these sites have not been compared. Samples from the nostrils and fecal collected on 9 occasions from 3 days to 3 years of age in 65 infants were cultured; 54 samples yielded S. aureus. The numbers of nasal and fecal S. aureus increased rapidly during the first weeks and were similar at 1 month of age (>40% of infants colonized). Thereafter, nasal carriage declined, while fecal carriage remained high during the first year of life. Individual strains were identified and their colonization patterns were related to their carriage of genes encoding adhesins and superantigenic toxins. Strains retrieved from both the nose and gut (n=44) of an infant were 4.5-times more likely to colonize long-term (≥3 weeks at both sites) than strains found only in the rectum/feces (n=56) or only in the nose (n=32) (P≤0.001). Gut colonization was significantly associated with carriage of the fnbA gene, and long-term colonization at either site was associated with carriage of fnbA and fnbB. In summary, gut colonization by S. aureus was more common than nasal carriage by S. aureus in the studied infants. Gut strains may provide a reservoir for invasive disease in vulnerable individuals. Fibronectin-binding adhesins and other virulence factors may facilitate commensal colonization and confer pathogenic potential. IMPORTANCE S. aureus may cause severe infections and frequently colonizes the nose. Nasal carriage of S. aureus increases three-fold the risk of invasive S. aureus infection. S. aureus is also commonly found in the gut microbiota of infants and young children. However, the relationships between the adhesins and other virulence factors of S. aureus strains and its abilities to colonize the nostrils and gut of infants are not well-understood. Our study explores the simultaneous colonization by S. aureus of the nasal and intestinal tracts of newborn infants, through 3 years of follow-up. We identify bacterial virulence traits that appear to facilitate persistent colonization of the nose and gut by S. aureus. This expands our current knowledge of the interplay between bacterial commensalism and pathogenicity. Moreover, it may contribute to the development of targeted strategies for combating S. aureus infection.

scholarly journals Phosphorylation of MgrA and Its Effect on Expression of the NorA and NorB Efflux Pumps of Staphylococcus aureus

2010 ◽  
Vol 192 (10) ◽  
pp. 2525-2534 ◽  
Author(s):  
Que Chi Truong-Bolduc ◽  
David C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Virulence Factors ◽  
Double Mutant ◽  
Efflux Pumps ◽  
Efflux Transporters ◽  
Global Regulator ◽  
Binding Assays ◽  
Genes Encoding ◽  
Gel Shift

ABSTRACT MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrAS110A-S113A bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates.

scholarly journals Intestinal microbiota and their metabolic contribution to type 2 diabetes and obesity

2021 ◽  
Author(s):  
A. L. Cunningham ◽  
J. W. Stephens ◽  
D. A. Harris
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Global Epidemic ◽  
Technological Advances ◽  
Diabetes And Obesity

AbstractObesity and type 2 diabetes mellitus (T2DM) are common, chronic metabolic disorders with associated significant long-term health problems at global epidemic levels. It is recognised that gut microbiota play a central role in maintaining host homeostasis and through technological advances in both animal and human models it is becoming clear that gut microbiota are heavily involved in key pathophysiological roles in the aetiology and progression of both conditions. This review will focus on current knowledge regarding microbiota interactions with short chain fatty acids, the host inflammatory response, signaling pathways, integrity of the intestinal barrier, the interaction of the gut-brain axis and the subsequent impact on the metabolic health of the host.

scholarly journals Genotypic diversity between surgical and nasal Staphylococcus aureus isolates

2020 ◽  
Author(s):  
Dongzhu Ma ◽  
Patrick L. Maher ◽  
Kimberly M. Brothers ◽  
Nathan J. Phillips ◽  
Deborah Simonetti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Joint Infection ◽  
Parallel Evolution ◽  
Genotypic Diversity ◽  
Nasal Carriage ◽  
Host Immune System ◽  
Host Status ◽  
Fibronectin Binding ◽  
Two Populations ◽  
Atypical Strains

AbstractStaphylococcus aureus is a common organism in periprosthetic joint infection (PJI). Little is known about S. aureus genetic diversity in PJI as compared to nasal carriage. We hypothesized PJI S. aureus strains would be associated with increased virulence as compared to those from nasal carriage. Whole genome sequencing and multilocus sequence typing (MLST) was performed to genotype these two populations at high resolution. MLST revealed a variety of genotypes in both populations but many belonged to the most common clonal complexes. In nasal cultures, 69% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 51% could be classified in these common clonal complexes. Remaining strains were atypical, and these atypical strains in PJI were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient. S. aureus isolated from nasal carriage and PJI specimens differ significantly, with the latter being more diverse. Strains associated with lower pathogenicity tended to be found in immunocompromised patients, suggesting the host immune system plays an important role in preventing PJI. Repeated mutations in S. aureus genes associated with extracellular matrix binding were identified suggesting an adaptive, parallel evolution in S. aureus during the development of PJI.

scholarly journals The purine biosynthesis regulator PurR moonlights as a virulence regulator in Staphylococcus aureus

2019 ◽  
Vol 116 (27) ◽  
pp. 13563-13572 ◽  
Author(s):  
William E. Sause ◽  
Divya Balasubramanian ◽  
Irnov Irnov ◽  
Richard Copin ◽  
Mitchell J. Sullivan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Ex Vivo ◽  
Purine Biosynthesis ◽  
In Vivo Studies ◽  
Human Neutrophils ◽  
Infection Models ◽  
Genes Encoding ◽  
Virulence Regulator

The pathogen Staphylococcus aureus colonizes and infects a variety of different sites within the human body. To adapt to these different environments, S. aureus relies on a complex and finely tuned regulatory network. While some of these networks have been well-elucidated, the functions of more than 50% of the transcriptional regulators in S. aureus remain unexplored. Here, we assess the contribution of the LacI family of metabolic regulators to staphylococcal virulence. We found that inactivating the purine biosynthesis regulator purR resulted in a strain that was acutely virulent in bloodstream infection models in mice and in ex vivo models using primary human neutrophils. Remarkably, these enhanced pathogenic traits are independent of purine biosynthesis, as the purR mutant was still highly virulent in the presence of mutations that disrupt PurR’s canonical role. Through the use of transcriptomics coupled with proteomics, we revealed that a number of virulence factors are differentially regulated in the absence of purR. Indeed, we demonstrate that PurR directly binds to the promoters of genes encoding virulence factors and to master regulators of virulence. These results guided us into further ex vivo and in vivo studies, where we discovered that S. aureus toxins drive the death of human phagocytes and mice, whereas the surface adhesin FnbA contributes to the increased bacterial burden observed in the purR mutant. Thus, S. aureus repurposes a metabolic regulator to directly control the expression of virulence factors, and by doing so, tempers its pathogenesis.

scholarly journals Prevalence of genes encoding extracellular virulence factors among meticillin-resistant Staphylococcus aureus isolates from the University Hospital, Olomouc, Czech Republic

2008 ◽  
Vol 57 (4) ◽  
pp. 403-410 ◽  
Author(s):  
P. Sauer ◽  
J. Síla ◽  
T. Štosová ◽  
R. Večeřová ◽  
P. Hejnar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Czech Republic ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Antibiotic Susceptibility ◽  
University Hospital ◽  
Virulence Determinants ◽  
Virulence Markers ◽  
Genes Encoding ◽  
The University

A rather fast and complicated progression of an infection caused by some strains of Staphylococcus aureus could be associated with the expression and co-action of virulence factor complexes in these strains. This study screened the antibiotic susceptibility and prevalence of virulence markers in isolates of meticillin-resistant S. aureus (MRSA) obtained from patients hospitalized at the University Hospital in Olomouc, Czech Republic. A total of 100 isolates was screened for 13 genes encoding extracellular virulence determinants (tst, pvl, eta, etb, sea, seb, sec, sed, see, seg, seh, sei and sej) and for their distribution in sample types. Eighty-nine isolates were positive for at least one of the genes. Genes for etb, pvl, see and seh were not detected in any of the MRSA isolates. No statistically significant differences in the occurrence of the determinants studied among sample types were found.

scholarly journals Long-term cortisol levels are not associated with nasal carriage of Staphylococcus aureus

2011 ◽  
Vol 31 (1) ◽  
pp. 97-100 ◽  
Author(s):  
L. Manenschijn ◽  
A. M. Jetten ◽  
W. J. B. van Wamel ◽  
M. Tavakol ◽  
J. W. Koper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Nasal Carriage ◽  
Cortisol Levels

scholarly journals Going through phages: A Computational approach to Revealing the role of prophage in Staphylococcus aureus

2021 ◽  
Author(s):  
Tyrome Steven Sweet ◽  
Suzanne Sindi ◽  
Mark Sistrom
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Genome Evolution ◽  
Virulence Factors ◽  
Rapid Growth ◽  
Computational Approach ◽  
Computational Pipeline ◽  
Genes Encoding

Prophages have important roles in virulence, antibiotic resistance and genome evolution in Staphylococcus aureus. Rapid growth in the number of sequenced S. aureus genomes allows for an investigation of prophage sequences in S. aureus at an unprecedented scale. We developed a computational pipeline to detect and analyze prophage sequences in nearly 10,011 S. aureus genomes, discovering thousands of putative prophage sequences with genes encoding virulence factors and antibiotic resistance.

scholarly journals Mapping the Global Network of Extracellular Protease Regulation in Staphylococcus aureus

2019 ◽  
Author(s):  
Brittney D. Gimza ◽  
Maria I. Larias ◽  
Bridget G. Budny ◽  
Lindsey N. Shaw
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Global Network ◽  
Protease Production ◽  
Secondary Circuit ◽  
Pathogenic Potential ◽  
Regulatory Circuit ◽  
Primary Network ◽  
The Impact ◽  
Protease Expression

AbstractA primary function of the extracellular proteases of Staphylococcus aureus is to control the progression of infection by selectively modulating the stability of virulence factors. Consequently, a regulatory network exists to titrate protease abundance/activity, to influence accumulation, or lack thereof, of individual virulence factors. Herein, we comprehensively map this system, exploring regulation of the four protease loci by known and novel factors. In so doing, we determine that seven major elements (SarS, SarR, Rot, MgrA, CodY, SaeR, and SarA) form the primary network of control, with the latter three being the most powerful. We note that expression of aureolysin is largely repressed by these factors, whilst the spl operon is subject to the strongest upregulation of any protease loci, particularly by SarR and SaeR. Furthermore, when exploring scpA expression, we find it to be profoundly influenced in opposing fashions by SarA (repressor) and SarR (activator). We also present the screening of >100 regulator mutants of S. aureus, identifying 7 additional factors (ArgR2, AtlR, MntR, Rex, XdrA, Rbf, and SarU) that form a secondary circuit of protease control. Primarily these elements serve as activators, although we reveal XdrA as a new repressor of protease expression. With the exception or ArgR2, each of the new effectors appear to work through the primary network of regulation to influence protease production. Collectively, we present a comprehensive regulatory circuit that emphasizes the complexity of protease regulation and suggest that its existence speaks to the importance of these enzymes to S. aureus physiology and pathogenic potential.ImportanceThe complex regulatory role of the proteases necessitates very tight coordination and control of their expression. Whilst this process has been well studied, a major oversight has been the consideration of proteases as a single entity, rather than 10 enzymes produced from four different promoters. As such, in this study we comprehensively characterized the regulation of each protease promoter, discovering vast differences in the way each protease operon is controlled. Additionally, we broaden the picture of protease regulation using a global screen to identify novel loci controlling protease activity, uncovering a cadre of new effectors of protease expression. The impact of these elements on the activity of proteases and known regulators was characterized producing a comprehensive regulatory circuit that emphasizes the complexity of protease regulation in Staphylococcus aureus.

scholarly journals Effects of four antibiotics on the diversity of the intestinal microbiota

2021 ◽  
Author(s):  
Ce Huang ◽  
Shengyu Feng ◽  
Fengjiao Huo ◽  
Hailiang Liu
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Rrna Gene ◽  
Oral Antibiotics ◽  
Negative Effects ◽  
Pathogenic Potential ◽  
Intestinal Pathogens

ABSTRACTOral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, which increases the risk of colonization with intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and potentially pathogenic bacteria under conditions of gut microbiota dysbiosis. Additionally, it is controversial whether the effects of antibiotics on the gut microbiota are temporary or permanent. In this study, we used 16S rRNA gene sequencing to evaluate the short-term and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota by analyzing changes in the relative numbers of potentially beneficial and potentially pathogenic bacteria. We found that the changes in the intestinal microbiota reflected the antibiotics’ mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between the different bacterial communities. Thus, destruction of bacteria with beneficial potential increased the abundance of bacteria with pathogenic potential. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota and the relative proportions of bacteria with beneficial potential and bacteria with pathogenic potential, thereby increasing the risk of host disease.

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