RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP

Armbruster, Chelsie E.; Pang, Bing; Juneau, Richard A.; Perez, Antonia C.; Weimer, Kristin E. D.; Swords, W. Edward

doi:10.1111/j.1365-2958.2011.07831.x

Cited by 68 publications

(80 citation statements)

References 56 publications

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“…AI-2 uptake may result from a currently unknown AI-2 receptor in the RA genome which, just like the LsrB homologues in Salmonella typhimurium and E. coli or LuxP in V. harveyi [22], are involved in AI-2 uptake [23,24]. Moreover, one new gene, rbsB, which was associated with AI-2 uptake, has been identified in Haemophilus influenzae [25]. Hence, we speculate that potential AI-2 receptors might exist in RA and play roles in AI-2 uptake.…”

Section: Discussionmentioning

confidence: 96%

Riemerella anatipestifer lacks luxS, but can uptake exogenous autoinducer-2 to regulate biofilm formation

Han

Liu

Fan

et al. 2015

Research in Microbiology

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Section: Discussionmentioning

confidence: 96%

Riemerella anatipestifer lacks luxS, but can uptake exogenous autoinducer-2 to regulate biofilm formation

Han

Liu

Fan

et al. 2015

Research in Microbiology

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“…NTHI can cause chronic otitis media infection in the chinchilla, during which bacteria persist within biofilms for weeks or even months (19,20). Therefore, we used the chinchilla infection model to assess the role(s) of pdgX and/or hktE in persistence of NTHI within the middle-ear chamber.…”

Section: Resultsmentioning

confidence: 99%

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

et al. 2015

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Nontypeable Haemophilus influenzae (NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded by hktE) and a bifunctional peroxiredoxin-glutaredoxin (encoded by pdgX) in resistance of NTHI to oxidants and persistence in vivo. Isogenic NTHI strain 86-028NP mutants lacking hktE and pdgX had increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed that pdgX and hktE were important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilms in vivo. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs. Nontypeable Haemophilus influenzae (NTHI) is a common resident of the human upper airways, where carriage is usually asymptomatic (1). In patients with mucociliary clearance deficits, NTHI can also cause opportunistic infections; these include airway infections in patients with chronic obstructive pulmonary disease (COPD) (2) and otitis media infections in children (3). These infections are often chronic and recurrent in nature, and it is now well established that the persistent NTHI populations reside within biofilm communities on the airway surface (4-6). NTHI persists in the chinchilla middle ear even in the face of immune effectors that contribute to the biofilm structure, such as neutrophils and neutrophil extracellular traps (NETs) (7). These NETs can have phagocytosis-independent antimicrobial activity that involves trapping of invading microorganisms by decondensed chromatin and microbicides from the neutrophil granules, which decorate the DNA NET lattice (8, 9). Our recent work shows that NTHI bacteria survive within NETs (7) and are resistant to extracellular killing within the NET and phagocytic killing by incoming neutrophils (10).The objective of the present study was to test the relevance of peroxiredoxin-glutaredoxin (encoded by pdgX) and catalase (encoded by hktE) in opportunistic infections caused by NTHI strain 86-028NP. The data support the conclusion that these factors have overlapping roles in resistance of NTHI to oxidative killing and thus promote survival of NTHI within NET structures and persistence in vivo in the lung and middle ear. MATERIALS AND METHODSBacterial culture and manipulation. A ...

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“…Soluble mediators, released by bacteria, modulate the composition of NTHI lipooligosaccharides that effects biofilm maturation and persistence in vivo (144). Swords and colleagues showed that RbsB participates as a quorum regulated protein required for uptake of and response to the signaling molecule AI-2 (145). The consequence of a tryptophanase driven increase in indole on biofilm inhibition may be diminished through increased transport of AI-2.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Harrison

Dubois

John-Williams

et al. 2016

Molecular & Cellular Proteomics

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A thorough understanding of the molecular details of the interactions between bacteria and host are critical to ultimately prevent disease. Recent technological advances allow simultaneous analysis of host and bacterial protein and metabolic profiles from a single small tissue sample to provide insight into pathogenesis. We used the chinchilla model of human otitis media to determine, for the first time, the most expansive delineation of global changes in protein and metabolite profiles during an experimentally induced disease. After 48 h of infection with nontypeable Haemophilus influenzae, middle ear tissue lysates were analyzed by high-resolution quantitative two-dimensional liquid chromatography-tandem mass spectrometry. Dynamic changes in 105 chinchilla proteins and 66 metabolites define the early proteomic and metabolomic signature of otitis media. Our studies indicate that establishment of disease coincides with actin morphogenesis, suppression of inflammatory mediators, and bacterial aerobic respiration. We validated the observed increase in the actin-remodeling complex, Arp2/3, and experimentally showed a role for Arp2/3 in nontypeable Haemophilus influenzae invasion. Direct inhibition of actin branch morphology altered bacterial invasion into host epithelial cells, and is supportive of our efforts to use the information gathered to modify outcomes of disease. The twenty-eight nontypeable Haemophilus influenzae proteins identified participate in carbohydrate and amino acid metabolism, redox homeostasis, and include cell wall-associated metabolic proteins. Quantitative characterization of the molecular signatures of infection will redefine our understanding of host response driven developmental changes during pathogenesis. These data represent the first comprehensive study of host protein and metabolite profiles in vivo in response to infection and show the feasibility of extensive characterization of host protein profiles during disease. Identification of novel protein targets and metabolic biomarkers will advance development of therapeutic and diagnostic options for treatment of disease. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052498, 1117-1138, 2016.Our current understanding of the global changes that occur during infection is primarily based upon transcriptional profiles of either the host or the bacteria. However, a significant component of disease progression is dependent upon posttranscriptional processes. Recent advances in the application of two-dimensional tandem mass spectrometry have dramatically increased sensitivity to allow simultaneous analyses of multiple molecules from very small biological samples. In this study, we report the comprehensive proteomic and metabolomic profiling of middle ear tissues using samples that are smaller than those typically obtained from a human biopsy. Proteomic and metabolomic analyses of samples as small as biopsies will revolutionize the elucidation of the mechanisms From the

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RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP

Cited by 68 publications

References 56 publications

Riemerella anatipestifer lacks luxS, but can uptake exogenous autoinducer-2 to regulate biofilm formation

Riemerella anatipestifer lacks luxS, but can uptake exogenous autoinducer-2 to regulate biofilm formation

Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

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