scholarly journals Lack of nutritional immunity in diabetic skin infections promotes Staphylococcus aureus virulence

2020 ◽  
Vol 6 (46) ◽  
pp. eabc5569
Author(s):  
Lance R. Thurlow ◽  
Amelia C. Stephens ◽  
Kelly E. Hurley ◽  
Anthony R. Richardson
Keyword(s):  
Staphylococcus Aureus ◽  
High Efficiency ◽  
Limited Resource ◽  
Glucose Consumption ◽  
Glucose Transporters ◽  
Nutritional Immunity ◽  
Virulence Potential ◽  
Invasive Infections ◽  
Virulence Factor Production ◽  
Excess Glucose

Elevated blood/tissue glucose is a hallmark feature of advanced diabetes, and people with diabetes are prone to more frequent and invasive infections with Staphylococcus aureus. Phagocytes must markedly increase glucose consumption during infection to generate and oxidative burst and kill invading bacteria. Similarly, glucose is essential for S. aureus survival in an infection and competition with the host, for this limited resource is reminiscent of nutritional immunity. Here, we show that infiltrating phagocytes do not express their high-efficiency glucose transporters in modeled diabetic infections, resulting in a diminished respiratory burst and increased glucose availability for S. aureus. We show that excess glucose in these hyperglycemic abscesses significantly enhances S. aureus virulence potential, resulting in worse infection outcomes. Last, we show that two glucose transporters recently acquired by S. aureus are essential for excess virulence factor production and the concomitant increase in disease severity in hyperglycemic infections.

scholarly journals Host- and Tissue-Specific Pathogenic Traits of Staphylococcus aureus

2005 ◽  
Vol 187 (13) ◽  
pp. 4584-4591 ◽  
Author(s):  
Willem B. van Leeuwen ◽  
Damian C. Melles ◽  
Alwaleed Alaidan ◽  
Mohammed Al-Ahdal ◽  
Hélène A. M. Boelens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Toxic Shock Syndrome ◽  
Virulence Genes ◽  
Close Contact ◽  
Toxic Shock ◽  
Gene Encoding ◽  
Virulence Potential ◽  
Invasive Infections ◽  
Toxic Shock Syndrome Toxin ◽  
Syndrome Protein

ABSTRACT Comparative genomics were used to assess genetic differences between Staphylococcus aureus strains derived from infected animals versus colonized or infected humans. A total of 77 veterinary isolates were genetically characterized by high-throughput amplified fragment length polymorphism (AFLP). Bacterial genotypes were introduced in a large AFLP database containing similar information for 1,056 human S. aureus strains. All S. aureus strains isolated from animals in close contact with humans (e.g., pet animals) were predominantly classified in one of the five main clusters of the AFLP database (cluster I). In essence, mastitis-associated strains from animals were categorized separately (cluster IVa) and cosegregated with bacteremia-associated strains from humans. Distribution of only 2 out of 10 different virulence genes differed across the clusters. The gene encoding the toxic shock syndrome protein (tst) was more often encountered among veterinary strains (P < 0.0001) and even more in the mastitis-related strains (P<0.0001) compared to human isolate results. The gene encoding the collagen binding protein (cna) was rarely detected among invasive human strains. The virulence potential, as indicated by the number of virulence genes per strain, did not differ significantly between the human- and animal-related strains. Our data show that invasive infections in pets and humans are usually due to S. aureus strains with the same genetic background. Mastitis-associated S. aureus isolated in diverse farm animal species form a distinct genetic cluster, characterized by an overrepresentation of the toxic shock syndrome toxin superantigen-encoding gene.

scholarly journals 855. Significance of Invasive Infections due to Methicillin Sensitive Staphylococcus aureus in the neonatal population

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S468-S468
Author(s):  
Mariawy Riollano ◽  
Deena Altman ◽  
shanna kowalsky ◽  
Stephanie Pan
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Characteristics ◽  
Invasive Disease ◽  
Control Measures ◽  
Invasive Infection ◽  
Single Center ◽  
Infection Control Measures ◽  
Invasive Infections ◽  
Mrsa Colonization ◽  
Neonatal Population

Abstract Background Staphylococcus aureus is a well-known cause of hospital acquired infections. Methicillin resistant staphylococcus aureus (MRSA) colonization is a recognized risk factor for invasive infections. The neonatal population in the intensive care unit (NICU) is particularly vulnerable to these types of infections, resulting in high mortality and morbidity. However, only scant data is available to establish the risk for invasive disease in patients with Methicillin sensitive staphylococcus aureus (MSSA). As a result, surveillance and prevention strategies are only address for MRSA colonization. Here, we describe the clinical characteristics of S. aureus colonized patients identified in late 2018 during transmission events in a single center NICU. As a result of the targeted surveillance investigation for MRSA infection control measures, S. aureus colonization was stratified, and we were able to compare the differences in invasive disease between MRSA and MSSA. Methods This is a retrospective chart review of the 47 colonized patients identified during October 2018- January 2019 SA transmission events in single center NICU. Risk factors, clinical characteristics, and the hospital course of these cases, including the proportion of invasive illness were reviewed. Results We found that most clinical characteristic, risk factors, and hospital course were the same between MRSA and MSSA colonized infants (p values &gt; 0.05). Additionally, there was no difference in the proportion of invasive infection between MRSA and MSSA colonized patients (p value &gt; 0.05). The type of invasive infections identified were SSTI, bacteremia, and osteomyelitis. Conclusion The proportion of invasive infection was the same in MSSA and MRSA colonized patients. This data provides us with supportive material for future recommendations of infection control measures for MSSA colonized patients. Disclosures All Authors: No reported disclosures

"Panton-Valentine leukocidine"-producerende Staphylococcus aureus als belangrijke pathogeen voor purulente huidinfecties

2021 ◽  
Author(s):  
L. DE LAET ◽  
M. SCHELLEN ◽  
M. DEPYPERE ◽  
D. MARTINY ◽  
M. HALLIN ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Adult Population ◽  
Reference Laboratory ◽  
Skin Infections ◽  
National Guidelines ◽  
Toxin Detection ◽  
Reference Centre ◽  
Invasive Infections ◽  
Panton Valentine Leukocidin ◽  
Valentine Leukocidin

“Panton-Valentine leukocidin”- producing Staphylococcus aureus is an important pathogen of purulent skin and soft-tissue infections Staphylococcus aureus (S. aureus) colonises the skin, nose or throat in 20% to 30% of the adult population and is the most common pathogen causing mild to moderate skin infections. Panton-Valentine leukocidin (PVL) is an important virulence factor for S. aureus and plays a potential role in the pathogenesis of dermal necrosis. PVL is strongly associated with recurrent purulent skin infections and frequent need for surgical drainage. It is comparatively less common in colonisation and invasive infections (such as pneumonia, musculoskeletal disease and bacteraemia). The number of community-acquired PVLP-SA clones in Belgium remains stable since 2014. PVL-toxin detection in Belgium is limited to the National Reference Centre for S. aureus (LHUB-ULB, Brussels). Because of the limited indications for toxin testing and lack of impact on antibiotic therapy, there is currently no need for PVL-toxin detection outside the reference laboratory. On the other hand, increased awareness can lead to more efficient and systematic decolonisation policies and thereby reduce the risk of recurrent skin infections or outbreaks in (healthcare) institutions. In this case report followed by a literature review, we would like to inform all interested and involved clinicians (general practitioners, dermatologists, internists, paediatricians) about the national guidelines for PVL-toxin detection and the associated approach.

scholarly journals Total Synthesis of Xanthoangelol B and Its Various Fragments: Toward Inhibition of Virulence Factor Production of Staphylococcus aureus

2018 ◽  
Vol 61 (23) ◽  
pp. 10473-10487 ◽  
Author(s):  
Pushpak Mizar ◽  
Rekha Arya ◽  
Truc Kim ◽  
Soyoung Cha ◽  
Kyoung-Seok Ryu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Total Synthesis ◽  
Virulence Factor ◽  
Factor Production ◽  
Virulence Factor Production

scholarly journals The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 360
Author(s):  
Janina Treffon ◽  
Sarah Ann Fotiadis ◽  
Sarah van Alen ◽  
Karsten Becker ◽  
Barbara C. Kahl
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Airway Epithelial Cells ◽  
Farm Animals ◽  
Airway Epithelial ◽  
Methicillin Resistant ◽  
Virulence Potential ◽  
Airway Infections ◽  
Severe Infections

Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

scholarly journals Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Paola K. Párraga Solórzano ◽  
Jiangwei Yao ◽  
Charles O. Rock ◽  
Thomas E. Kehl-Fie
Keyword(s):  
Staphylococcus Aureus ◽  
Metabolic Flux ◽  
Bacterial Species ◽  
Critical Role ◽  
Dependent Manner ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Nutritional Immunity ◽  
Two Component

ABSTRACT During infection, bacteria use two-component signal transduction systems to sense and adapt to the dynamic host environment. Despite critically contributing to infection, the activating signals of most of these regulators remain unknown. This also applies to the Staphylococcus aureus ArlRS two-component system, which contributes to virulence by coordinating the production of toxins, adhesins, and a metabolic response that enables the bacterium to overcome host-imposed manganese starvation. Restricting the availability of essential transition metals, a strategy known as nutritional immunity, constitutes a critical defense against infection. In this work, expression analysis revealed that manganese starvation imposed by the immune effector calprotectin or by the absence of glycolytic substrates activates ArlRS. Manganese starvation imposed by calprotectin also activated the ArlRS system even when glycolytic substrates were present. A combination of metabolomics, mutational analysis, and metabolic feeding experiments revealed that ArlRS is activated by alterations in metabolic flux occurring in the latter half of the glycolytic pathway. Moreover, calprotectin was found to induce expression of staphylococcal leukocidins in an ArlRS-dependent manner. These studies indicated that ArlRS is a metabolic sensor that allows S. aureus to integrate multiple environmental stresses that alter glycolytic flux to coordinate an antihost response and to adapt to manganese starvation. They also established that the latter half of glycolysis represents a checkpoint to monitor metabolic state in S. aureus. Altogether, these findings contribute to understanding how invading pathogens, such as S. aureus, adapt to the host during infection and suggest the existence of similar mechanisms in other bacterial species. IMPORTANCE Two-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a Staphylococcus aureus global regulator that contributes to virulence and to resisting host-mediated restriction of essential nutrients, such as manganese. In this report, we demonstrate that manganese starvation and the absence of glycolytic substrates activate ArlRS. Further investigations revealed that ArlRS is activated when the latter half of glycolysis is disrupted, suggesting that S. aureus monitors flux through the second half of this pathway. Host-imposed manganese starvation also induced the expression of pore-forming toxins in an ArlRS-dependent manner. Cumulatively, this work reveals that ArlRS acts as a sensor that links nutritional status, cellular metabolism, and virulence regulation.

scholarly journals Panton–Valentine leukocidin Staphylococcus aureus osteomyelitis of the adult tibia – a case report

2010 ◽  
Vol 92 (2) ◽  
pp. e17-e19 ◽  
Author(s):  
MJ Hall ◽  
JA Steer ◽  
J Keenan
Keyword(s):  
Staphylococcus Aureus ◽  
Case Report ◽  
Soft Tissue ◽  
Surgical Management ◽  
Adult Male ◽  
Soft Tissue Infections ◽  
Musculoskeletal Infection ◽  
Invasive Infections ◽  
Panton Valentine Leukocidin ◽  
Valentine Leukocidin

Panton–Valentine leukocidin toxin producing Staphylococcus aureus (PVLSA) is known to be responsible for recurrent soft tissue infections and more serious invasive infections including necrotising pneumonia, pyomyositis, and osteomyelitis. Most reported cases involving musculoskeletal infection in adults are associated with methicillin-resistant S. aureus (MRSA) PVL-producing strains. We present the case of an adult male with PVL toxin–producing methicillin-sensitive S. aureus (MSSA) osteomyelitis of the tibia which has not previously been described in adults and highlight issues of recognition, treatment, and surgical management of PVLSA osteomyelitis.

scholarly journals 554. The Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus Causing Bacteremia in Hiroshima, Japan During 2008–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S263-S263
Author(s):  
Hiroki Kitagawa ◽  
Junzo Hisatsune ◽  
Hiroki Ohge ◽  
Motoyuki Sugai
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sccmec Type ◽  
University Hospital ◽  
Methicillin Resistant ◽  
Type Iv ◽  
Time Period ◽  
Invasive Infections ◽  
Toxic Shock Syndrome Toxin ◽  
Mrsa Strains

Abstract Background Recently, the Japanese intrinsic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone (CA-MRSA/J), classified as sequence type (ST) 8 carrying staphylococcal cassette chromosome mec (SCCmec) type IVl (ST8-IVl), has been identified that causes invasive infections similar to those of USA300 clone. However, epidemiological information regarding epidemic CA-MRSA clones is limited in Japan. This study was performed to investigate the changing epidemiology of MRSA causing bacteremia in Japan. Methods We performed whole-genome sequencing of MRSA isolates causing bacteremia at Hiroshima University Hospital between January 2008 and December 2017. MRSA isolates were subjected to multilocus sequence typing, SCCmec typing and were analyzed for virulence factors. Clinical data of patients with MRSA bacteremia were analyzed. Results A total of 193 MRSA strains causing bacteremia were identified during the study period. Among these, most belonged to ST764-IIa (30%; 59 of 193) and ST5-IIa (26.9%; 52 of 193). The proportion of ST5-IIa MRSA decreased from 39.6% (42 of 106) in 2008–2012 to 11.5% (10 of 87) in 2013–2017, and that of ST764-IIa MRSA increased from 23.6% (25 of 106) to 39.1% (34 of 87) in the same time period. The proportion of CA-MRSA (MRSA carrying SCCmec type IV or V) increased from 28.3% (30 of 106) in 2008–2012 to 42.5% (37 of 87) in 2013–2017. In CA-MRSA strains, clonal complex (CC) 8-IV MRSA was predominant (76.1%; 51 of 67). Those belonging to CC8-IV MRSA isolates were ST380-IVc (18 of 51), ST8-IVl (CA-MRSA/J; 15 of 51), ST8-IVj (15 of 51), ST8-IVa (2 of 51), and ST4803-IVl (1 of 51). The rate of hospital-onset infections of ST380-IVc, ST8-IVl, and ST8-IVj were 83.3%, 46.7%, and 60%, respectively. In CA-MRSA/J strains, including their variants (e.g., ST4803-IVl), 14 of 16 strains (87.5%) carried genes for toxic shock syndrome toxin (tst-1), enterotoxin C (sec), and enterotoxin L (sel), while none of the ST380-IVc and ST8-IVj MRSA strains carried these genes. Conclusion During the study period of 10 years, predominant ST5-IIa MRSA causing hospital-onset infections was replaced by ST764-IIa MRSA. In CA-MRSA clone, ST380-IVc, ST8-IVl (CA-MRSA/J), and ST8-IVj were dominant and have already spread to the healthcare environment. Disclosures All authors: No reported disclosures.

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