scholarly journals Long term nasopharyngeal colonization by Staphylococcus aureus determinants of adaptation

2021 ◽  
Author(s):  
Breno A B Salgado ◽  
Elaine Waters ◽  
Josephine Chantale Moran ◽  
Aras Kadioglu ◽  
Malcolm James Horsburgh
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Responses ◽  
Infection Model ◽  
Nasal Colonization ◽  
Nasopharyngeal Colonization ◽  
Peptidoglycan Synthesis ◽  
Selection For ◽  
Repair Genes ◽  
Key Pathways

Staphylococcus aureus nasal colonization is a risk factor for infection. A large proportion of the population are identified as potential S. aureus carriers yet we only partially understand the repertoire of genetic factors that promote long-term nasal colonization. Here we present a novel murine model of nasopharyngeal colonization that requires a low S. aureus inoculum and is amenable to experimental evolution approaches. We used this model to experimentally evolve S. aureus using successive passages in the nasopharynx to identify those genetic loci under selection. After 3 cycles of colonization, mutations were identified in mannitol, sorbitol, arginine, nitrite and lactate metabolism genes promoting key pathways in nasal colonization. Stress responses were identified as being under selective pressure, with mutations in DNA repair genes including dnaJ and recF and key stress response genes clpL, rpoB and ahpF . Peptidoglycan synthesis pathway genes also revealed mutations indicating potential selection for alteration of the cell surface. The infection model used here is versatile to assist decolonization and persistence studies.

scholarly journals Targeting Surface Protein SasX by Active and Passive Vaccination To Reduce Staphylococcus aureus Colonization and Infection

2015 ◽  
Vol 83 (5) ◽  
pp. 2168-2174 ◽  
Author(s):  
Qian Liu ◽  
Xin Du ◽  
Xufen Hong ◽  
Tianming Li ◽  
Bing Zheng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Passive Immunization ◽  
Surface Protein ◽  
Lung Infection ◽  
Active Immunization ◽  
Human Neutrophils ◽  
Infection Model ◽  
Nasal Colonization ◽  
Content Type ◽  
Infection Models

SasX is a recently described surface protein ofStaphylococcus aureusthat is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused byS. aureusin a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reducedS. aureuscolonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility ofS. aureusto killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection bysasX-positive epidemic strains ofS. aureus.

scholarly journals Persistent Staphylococcus aureus Isolates from Two Independent Cases of Bacteremia Display Increased Bacterial Fitness and Novel Immune Evasion Phenotypes

2015 ◽  
Vol 83 (8) ◽  
pp. 3311-3324 ◽  
Author(s):  
R. L. Richards ◽  
R. D. Haigh ◽  
B. Pascoe ◽  
S. K. Sheppard ◽  
F. Price ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Stress Responses ◽  
Galleria Mellonella ◽  
Whole Genome Sequence ◽  
Infection Model ◽  
Phenotypic Traits ◽  
Host Immune System ◽  
Content Type ◽  
Bacterial Fitness

Staphylococcus aureusbacteremia cases are complicated by bacterial persistence and treatment failure despite the confirmedin vitrosusceptibility of the infecting strain to administered antibiotics. A high incidence of methicillin-resistantS. aureus(MRSA) bacteremia cases are classified as persistent and are associated with poorer patient outcomes. It is still unclear howS. aureusevades the host immune system and resists antibiotic treatment for the prolonged duration of a persistent infection. In this study, the genetic changes and associated phenotypic traits specific toS. aureuspersistent bacteremia were identified by comparing temporally dispersed isolates from persistent infections (persistent isolates) originating from two independent persistentS. aureusbacteremia cases with the initial infection isolates and with three resolvedS. aureusbacteremia isolates from the same genetic background. Several novel traits were associated specifically with both independent sets of persistentS. aureusisolates compared to both the initial isolates and the isolates from resolved infections (resolved isolates). These traits included (i) increased growth under nutrient-poor conditions; (ii) increased tolerance of iron toxicity; (iii) higher expression of cell surface proteins involved in immune evasion and stress responses; and (iv) attenuated virulence in aGalleria mellonellalarva infection model that was not associated with small-colony variation or metabolic dormancy such as had been seen previously. Whole-genome sequence analysis identified different single nucleotide mutations within themprFgenes of all the isolates with the adaptive persistence traits from both independent cases. Overall, our data indicate a novel role for MprF function during development ofS. aureuspersistence by increasing bacterial fitness and immune evasion.

scholarly journals Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5349
Author(s):  
Mayes Alswady-Hoff ◽  
Johanna Samulin Erdem ◽  
Santosh Phuyal ◽  
Oskar Knittelfelder ◽  
Animesh Sharma ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Health Effects ◽  
Stress Responses ◽  
Cell Stress ◽  
Lipid Classes ◽  
Long Term Effects ◽  
Cell Death Pathways ◽  
Pulmonary Epithelial Cells

There is little in vitro data available on long-term effects of TiO2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.

Infective endocarditis in patients who use IV drugs: a single centre cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Alraddadi ◽  
A Alsagheir ◽  
S Gao ◽  
K An ◽  
H Hronyecz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Long Term Outcomes ◽  
Replacement Surgery ◽  
Short Term Mortality ◽  
History Of ◽  
Short And Long Term ◽  
Baseline Characteristics

Abstract Background Managing endocarditis in intravenous drug use (IVDU) patients is challenging: unless patients successfully quit IVDU, the risk of re-infection is high. Clinicians often raise concerns with ethical and resource allocation principles when considering valve replacement surgery in this patient population. To help inform practice, we sought to determine the long-term outcomes of IVDU patients with endocarditis who underwent valve surgery in our center. Method After research ethics board approval, infective endocarditis cases managed surgically at our General Hospital between 2009 and 2018 were identified through the Cardiac Care Network. We reviewed patients' charts and included those with a history of IVDU in this study. We abstracted data on baseline characteristics, peri-operative course, short- and long-term outcomes. We report results using descriptive statistics. Results We identified 124 IVDU patients with surgically managed endocarditis. Mean age was 37 years (SD 11), 61% were females and 8% had redo surgery. During admission, 45% (n=56) of the patients had an embolic event: 63% pulmonary, 30% cerebral, 18% peripheral and 11% mesenteric. Causative organisms included Methicillin-Sensitive Staphylococcus Aureus (51%, n=63), Methicillin-Resistant Staphylococcus Aureus (15%, n=19), Streptococcus Viridans (2%, n=2), and others (31%, n=38). Emergency cardiac surgery was performed for 42% of patients (n=52). Most patients (84%) had single valve intervention: 53% tricuspid, 18% aortic and 13% mitral. Double valve interventions occurred in 15% (n=18). Overall, bioprosthetic replacement was most commonly chosen (79%, n=98). In-hospital mortality was 7% (n=8). Median length of stay in hospital was 13 days (IQR 8,21) and ICU 2 days (IQR 1,6). Mortality at longest available follow-up was 24% (n=30), with a median follow-up of 129 days (IQR 15,416). Valve reintervention rate was 11% (n=13) and readmission rate was 14% (n=17) at a median of 275 days (IQR 54,502). Conclusion Despite their critical condition, IVDU patients with endocarditis have good intra-hospital outcomes. Challenges occur after hospital discharge with loss of follow-up and high short-term mortality. IVDU relapse likely accounts for some of these issues. In-hospital and community comprehensive addiction management may improve these patients' outcomes beyond the surgical procedure. Annual rate 2009–2018 Funding Acknowledgement Type of funding source: None

scholarly journals The Effectiveness of Contact Precautions on Methicillin-Resistant Staphylococcus aureus in Long-term Care Across the United States

2019 ◽  
Vol 71 (7) ◽  
pp. 1676-1683 ◽  
Author(s):  
Daniel J Morgan ◽  
Min Zhan ◽  
Michihiko Goto ◽  
Carrie Franciscus ◽  
Bruce Alexander ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Long Term Care ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
The United States ◽  
Standard Precautions ◽  
Term Care ◽  
Contact Precautions ◽  
Care Facilities

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health care–associated infections in long-term care facilities (LTCFs). The Centers for Disease Control and Prevention recommends contact precautions for the prevention of MRSA within acute care facilities, which are being used within the United States Department of Veterans Affairs (VA) for LTCFs in a modified fashion. The impact of contact precautions in long-term care is unknown. Methods To evaluate whether contact precautions decreased MRSA acquisition in LTCFs, compared to standard precautions, we performed a retrospective effectiveness study (pre-post, with concurrent controls) using data from the VA health-care system from 1 January 2011 until 31 December 2015, 2 years before and after a 2013 policy recommending a more aggressive form of contact precautions. Results Across 75 414 patient admissions from 74 long-term care facilities in the United States, the overall unadjusted rate of MRSA acquisition was 2.6/1000 patient days. Patients were no more likely to acquire MRSA if they were cared for using standard precautions versus contact precautions in a multivariable, discrete time survival analysis, controlling for patient demographics, risk factors, and year of admission (odds ratio, 0.97; 95% confidence interval, .85–1.12; P = .71). Conclusions MRSA acquisition and infections were not impacted by the use of active surveillance and contact precautions in LTCFs in the VA.

scholarly journals Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition: study protocol for a randomized multicenter trial

Trials ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Michelle Gompelman ◽  
Yannick Wouters ◽  
Wietske Kievit ◽  
Joost Hopman ◽  
Heiman F. Wertheim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Parenteral Nutrition ◽  
Study Protocol ◽  
Multicenter Trial ◽  
Home Parenteral Nutrition ◽  
Nutrition Study
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