scholarly journals Immunometabolites Drive Bacterial Adaptation to the Airway

2021 ◽  
Vol 12 ◽  
Author(s):  
Kira L. Tomlinson ◽  
Alice S. Prince ◽  
Tania Wong Fok Lung
Keyword(s):  
Staphylococcus Aureus ◽  
Selection Pressure ◽  
Bacterial Virulence ◽  
Metabolic Flexibility ◽  
Virulence Determinants ◽  
Bacterial Isolates ◽  
Opportunistic Pathogens ◽  
Term Survival ◽  
Lung Infections

Pseudomonas aeruginosa and Staphylococcus aureus are both opportunistic pathogens that are frequently associated with chronic lung infections. While bacterial virulence determinants are critical in initiating infection, the metabolic flexibility of these bacteria promotes their persistence in the airway. Upon infection, these pathogens induce host immunometabolic reprogramming, resulting in an airway milieu replete with immune-signaling metabolites. These metabolites are often toxic to the bacteria and create a steep selection pressure for the emergence of bacterial isolates adapted for long-term survival in the inflamed lung. In this review, we discuss the main differences in the host immunometabolic response to P. aeruginosa and S. aureus, as well as how these pathogens alter their own metabolism to adapt to airway metabolites and cause persistent lung infections.

scholarly journals Self-sensitisation of Staphylococcus aureus to the antimicrobial factors found in human blood.

2021 ◽  
Author(s):  
Edward Douglas ◽  
Tarcisio Brignoli ◽  
Mario Recker ◽  
Eoin O'Brien ◽  
Rachel McLoughlin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Basis ◽  
Functional Verification ◽  
Invasive Infection ◽  
Opportunistic Pathogens ◽  
Dead End ◽  
Wall Teichoic Acids ◽  
Respiratory Microbiome ◽  
Gwas Approach

For opportunistic pathogens, the switch from a commensal to an invasive lifestyle is often considered an accidental event. But with plentiful opportunity, what leads one accidental event to result in an invasive infection, and another not to? And how much of this apparent stochasticity is driven by bacterial factors? To answer these questions, here we focussed on the major human pathogen Staphylococcus aureus, which can both reside asymptomatically as a member of our respiratory microbiome, or become invasive and cause infections as severe as bacteraemia. Survival upon exposure to the antibacterial factors found in serum is a critical aspect of their ability to cause bacteraemia, and across a collection of 300 clinical isolates we found there to be significant variability in this capability. Utilising a GWAS approach we have uncovered the genetic basis of much of this variability through the identification and functional verification of a number of new polymorphic loci that affect serum survival: tcaA, tarK, gntR, ilvC, arsB, yfhO, and pdhD. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, while simultaneously enhancing the sensitivity of S. aureus to serum through a process involving the ligation of wall teichoic acids into the cell wall. As blood-stage infections are a transmission dead-end for the bacteria, that S. aureus actively responds to serum to produce a protein which specifically limits their ability to survive in this environment demonstrates that the switch from the commensal to the invasive lifestyle is complex, and that TcaA may contribute to the long-term success of S. aureus by restricting the bacteria to their more readily transmissible commensal state.

Dry Stress and Survival Time of Enterobacter sakazakii and Other Enterobacteriaceae in Dehydrated Powdered Infant Formula

2007 ◽  
Vol 70 (9) ◽  
pp. 2111-2117 ◽  
Author(s):  
JUNCAL CAUBILLA BARRON ◽  
STEPHEN J. FORSYTHE
Keyword(s):  
Infant Formula ◽  
Salmonella Enteritidis ◽  
Klebsiella Oxytoca ◽  
Powdered Infant Formula ◽  
Enterobacter Sakazakii ◽  
Opportunistic Pathogens ◽  
Term Survival ◽  
E Coli ◽  
Sterile Product

Powdered infant formula is not a sterile product, and opportunistic pathogens could multiply in the reconstituted product, resulting in neonatal infections. In this study, the generation of sublethally injured Enterobacteriaceae during desiccation and their persistence in dehydrated powdered infant formula was assessed during a 2.5-year period. The study included 27 strains of Enterobacter sakazakii, Enterobacter cloacae, Salmonella Enteritidis, Citrobacter koseri, Citrobacter freundii, Escherichia coli, Escherichia vulneris, Pantoea spp., Klebsiella oxytoca, and Klebsiella pneumoniae. The number of sublethally injured cells generated during desiccation was lower for K. oxytoca, Pantoea spp., Salmonella Enteritidis, and capsulated strains of E. sakazakii than for the other Enterobacteriaceae. The Enterobacteriaceae could be divided into three groups with respect to their long-term survival in the desiccated state. C. freundii, C. koseri, and E. cloacae were no longer recoverable after 6 months, and Salmonella Enteritidis, K. pneumoniae, and E. coli could not be recovered after 15 months. Pantoea spp., K. oxytoca, and E. vulneris persisted over 2 years, and some capsulated strains of E. sakazakii were still recoverable after 2.5 years.

Long-term survival outcome following Staphylococcus aureus bacteraemia

2013 ◽  
Vol 18 (3) ◽  
pp. 102-109 ◽  
Author(s):  
Chong W. Ong ◽  
Jan L. Roberts ◽  
Peter J. Collignon
Keyword(s):  
Staphylococcus Aureus ◽  
Survival Outcome ◽  
Term Survival ◽  
Long Term Survival

scholarly journals ClpC affects the intracellular survival capacity of Staphylococcus aureus in non-professional phagocytic cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gubesh Gunaratnam ◽  
Lorena Tuchscherr ◽  
Mohamed I. Elhawy ◽  
Ralph Bertram ◽  
Janina Eisenbeis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Intracellular Survival ◽  
Host Cells ◽  
Virulence Determinants ◽  
Phagocytic Cells ◽  
Survival Capacity ◽  
Shock Proteins ◽  
Mutant Cells

Abstract Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During stress, bacteria synthesize a family of proteins known as heat shock proteins (HSPs) to facilitate adaptation and survival. Previously, we determined the Staphylococcus aureus HSP ClpC temporally alters bacterial metabolism and persistence. This led us to hypothesize that ClpC might alter intracellular survival. Inactivation of clpC in S. aureus strain DSM20231 significantly enhanced long-term intracellular survival in human epithelial (HaCaT) and endothelial (EA.hy926) cell lines, without markedly affecting adhesion or invasion. This phenotype was similar across a genetically diverse collection of S. aureus isolates, and was influenced by the toxin/antitoxin encoding locus mazEF. Importantly, MazEF alters mRNA synthesis and/or stability of S. aureus virulence determinants, indicating ClpC may act through the mRNA modulatory activity of MazEF. Transcriptional analyses of total RNAs isolated from intracellular DSM20231 and isogenic clpC mutant cells identified alterations in transcription of α-toxin (hla), protein A (spa), and RNAIII, consistent with the hypothesis that ClpC negatively affects the intracellular survival of S. aureus in non-professional phagocytic cells, via modulation of MazEF and Agr.

scholarly journals Staphylococcus aureus ClpC Is Required for Stress Resistance, Aconitase Activity, Growth Recovery, and Death

2005 ◽  
Vol 187 (13) ◽  
pp. 4488-4496 ◽  
Author(s):  
Indranil Chatterjee ◽  
Petra Becker ◽  
Matthias Grundmeier ◽  
Markus Bischoff ◽  
Greg A. Somerville ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Critical Role ◽  
Tca Cycle ◽  
Term Survival ◽  
Phase Recovery ◽  
Growth And Survival ◽  
Aconitase Activity

ABSTRACT The ability of Staphylococcus aureus to adapt to various conditions of stress is the result of a complex regulatory response. Previously, it has been demonstrated that Clp homologues are important for a variety of stress conditions, and our laboratory has shown that a clpC homologue was highly expressed in the S. aureus strain DSM20231 during biofilm formation relative to expression in planktonic cells. Persistence and long-term survival are a hallmark of biofilm-associated staphylococcal infections, as cure frequently fails even in the presence of bactericidal antimicrobials. To determine the role of clpC in this context, we performed metabolic, gene expression, and long-term growth and survival analyses of DSM20231 as well as an isogenic clpC allelic-replacement mutant, a sigB mutant, and a clpC sigB double mutant. As expected, the clpC mutant showed increased sensitivity to oxidative and heat stresses. Unanticipated, however, was the reduced expression of the tricarboxylic acid (TCA) cycle gene citB (encoding aconitase), resulting in the loss of aconitase activity and preventing the catabolization of acetate during the stationary phase. clpC inactivation abolished post-stationary-phase recovery but also resulted in significantly enhanced stationary-phase survival compared to that of the wild-type strain. These data demonstrate the critical role of the ClpC ATPase in regulating the TCA cycle and implicate ClpC as being important for recovery from the stationary phase and also for entering the death phase. Understanding the stationary- and post-stationary-phase recovery in S. aureus may have important clinical implications, as little is known about the mechanisms of long-term persistence of chronic S. aureus infections associated with formation of biofilms.

scholarly journals Variation in Biofilm-Forming Potential of Staphylococcus aureus from Clinical and Non-Clinical Sources

2021 ◽  
pp. 1-7
Author(s):  
K. Otokunefor ◽  
J. J. Jesutobi ◽  
O. E. Agbagwa
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
High Association ◽  
Term Survival ◽  
Medical Microbiology ◽  
Potential Marker ◽  
Port Harcourt

Introduction: Biofilm forming ability has been described as a potential marker of pathogenicity, particularly in Staphylococcus aureus. These biofilms are notable as an important contributor to virulence abilities, further aiding the producing strain in long term survival and resistance to antimicrobial agents. Regional data exploring biofilm forming ability of S. aureus from various sources is limited. This study therefore set out to explore variations in biofilm-forming potential of S. aureus from clinical and non-clinical sources. Place and Duration of Study: Medical Microbiology Laboratory, Department of Microbiology, University of Port Harcourt, Nigeria from August to October 2019. Methodology: Eighty five S. aureus clinical and non-clinical isolates were studied. Biofilm-forming potential was assessed using the Congo Red agar (CRA) method which describes both the presence and degree biofilm-forming potential. Results: Majority of isolates (65.9%) did not exhibit any biofilm-forming potential using the CRA method. Biofilm-forming potential however appeared source based with 100% of non-clinical S. aureus isolates lacking biofilm-forming potential, while 58% of clinical isolates showed biofilm-forming potential. A higher proportion (65.5%) of the clinical isolates exhibiting biofilm-forming potential where associated with strong biofilm-forming potential. Conclusion: This study reports a high association of biofilm-forming potential with S. aureus isolated from clinical rather than non-clinical settings. If this characteristic can indeed be used as a general marker of pathogenicity would however require more extensive studies.

scholarly journals Long-term survival following pericardiectomy for Staphylococcus aureus pericarditis in an HIV-positive drug user

1997 ◽  
Vol 18 (3) ◽  
pp. 526-527
Author(s):  
P. F. CURRIE ◽  
R. A. WRIGHT ◽  
C. CAMPANELLA ◽  
J. GRAY ◽  
N. A. BOON
Keyword(s):  
Staphylococcus Aureus ◽  
Drug User ◽  
Hiv Positive ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Results of surgical treatment of aortic root infection

Medicina ◽  
2009 ◽  
Vol 45 (9) ◽  
pp. 683
Author(s):  
Palmyra Semėnienė ◽  
Arimantas Grebelis ◽  
Gintaras Turkevičius ◽  
Giedrė Nogienė ◽  
Rasa Čypienė ◽  
...  
Keyword(s):  
Heart Failure ◽  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Mortality Rate ◽  
Aortic Root ◽  
Inhospital Mortality ◽  
Root Infection ◽  
Term Survival ◽  
Class Iv

Aim of the study. To investigate preoperative status and results of surgery of patients with confirmed diagnosis of aortic root infection. Materials and methods. We have analyzed data of 21 patients who were operated on at the Heart Surgery Center, Vilnius University, since January 1, 1997, till December 31, 2006. All these patients underwent surgery because of aortic root infection. The patients were aged 25–72 years (mean age, 53±14 years). There were 17 (80.9%) male patients. Sixteen patients (76%) preoperatively were in NYHA class IV. The abscesses of aortic root were confirmed preoperatively by means of esophageal echocardiography in 18 patients (86%). Blood cultures positive for Staphylococcus aureus were found in four patients (19.9%). All the patients underwent replacement of the aortic valve by mechanic prosthesis; one of these patients was reoperated because of persistent sepsis, and replacement of the aortic root with homograft was performed. The duration of follow-up of the patients was 1 to 10 years. Results. Inhospital mortality rate was 14.3%. The causes of death included sustained heart failure and sepsis. All these patients were in NYHA functional class IV preoperatively; one of these patients had culture positive for Staphylococcus aureus. Inhospital survival was 85.7%, one-year postoperative survival – 80.9%, and both five-year and ten-year survivals were 76.0%. The long-term survival was negatively influenced by recurrent infective endocarditis, heart failure, and age. Death occurred in 1 patient (11.1%) of the 9 patients who at the time of surgery were younger than 50 years and 4 patients (33.3%) of the 12 who were older than 50 years at the time of operation. Conclusions. The infection of aortic root is not common pathology; however, it is a complicated disease. Esophageal echocardiography is an informative method while diagnosing aortic root abscesses. The inhospital mortality is increased by the heart failure persisting after the operation and sepsis. The long-term survival is decreased by preoperative infective endocarditis of the prosthesis and heart failure. The mortality rate of patients older than 50 years is 3-fold higher than mortality rate of younger ones.

scholarly journals Small molecules with antibiofilm, antivirulence and antibiotic synergy activities againstPseudomonas aeruginosa

2016 ◽  
Author(s):  
Erik van Tilburg Bernardes ◽  
Laetitia Charron-Mazenod ◽  
David Reading ◽  
Shauna L. Reckseidler-Zenteno ◽  
Shawn Lewenza
Keyword(s):  
Cystic Fibrosis ◽  
Extracellular Matrix ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Small Molecules ◽  
Biofilm Formation ◽  
Chronic Infections ◽  
Term Survival ◽  
Lung Infections

AbstractBiofilm formation is a universal bacterial strategy for long-term survival in nature and during infections. Biofilms are dense microbial communities enmeshed within a polymeric extracellular matrix that protects bacteria from antibiotic exposure and the immune system and thus contribute to chronic infections.Pseudomonas aeruginosais an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in Cystic Fibrosis (CF) patients. The extracellular matrix ofP. aeruginosabiofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and non-mucoid isolates ofP. aeruginosaproduces the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation and immune evasion. Given the central importance of the Pel and Psl EPS in biofilm structure, they are attractive targets for novel anti-infective compounds. In this study we used a high throughput gene expression screen to identify compounds that repress expression ofpelandpslgenes as measured by transcriptionalluxfusions. Testing of thepel/pslrepressors demonstrated an antibiofilm activity against microplate and flow chamber biofilms formed by wild type and hyperbiofilm forming strains. To determine the potential role of EPS in virulence, mutants inpel/pslwere shown to have reduced virulence in the feeding behavior and slow killing virulence assays inCaenorhabditis elegans. The antibiofilm molecules also reducedP. aeruginosaPAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds were synergistic in killingP. aeruginosabiofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronicP. aeruginosainfections.Author summaryBacteria use the strategy of growing as a biofilm to promote long-term survival and therefore to cause chronic infections. One of the best examples isPseudomonas aeruginosaand the chronic lung infections in individuals with Cystic Fibrosis (CF). Biofilms are generally a dense community of bacteria enmeshed in an extracellular matrix that protects bacteria from numerous environmental stresses, including antibiotics and the immune system. In this study we developed an approach to identifyP. aeruginosabiofilm inhibitors by repressing the production of the matrix exopolysaccharide (EPS) polymers. Bacteria treated with compounds and then fed to the nematode also had showed reduced virulence by promoting nematode survival. To tackle the problem of biofilm tolerance of antibiotics, the compounds identified here also had the beneficial property of increasing the biofilm sensitivity to different classes of antibiotics. The compounds disarm bacteria but they do not kill or limit growth like antibiotics. We provide further support that disarmingP. aeruginosamay be a critical anti-infective strategy that limits the development of antibiotic resistance, and provides a new way for treating chronic infections.

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