Imaging mass spectrometry for assessing temporal proteomics: Analysis of calprotectin in <i>Acinetobacter baumannii</i> pulmonary infection

Moore, Jessica L.; Becker, Kyle W.; Nicklay, Joshua J.; Boyd, Kelli L.; Skaar, Eric P.; Caprioli, Richard M.

doi:10.1002/pmic.201300046

Cited by 48 publications

(52 citation statements)

References 52 publications

(60 reference statements)

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“…All animal experiments were approved by the Vanderbilt University Institutional Animal Care and Use Committee. The murine model of A. baumannii pneumonia was performed as previously described (44)(45)(46)(47)(48)(49). Briefly, Ab17978 bacteria were back-diluted 1:1,000 from an overnight culture and grown for 3.5 h at 37°C with shaking, washed twice with cold phosphate-buffered saline (PBS), and resuspended in PBS at an appropriate cell density for infection.…”

Section: Methodsmentioning

confidence: 99%

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

et al. 2017

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The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor capable of recognizing multiple pathogen-associated and dangerassociated molecular patterns that contributes to the initiation and potentiation of inflammation in many disease processes. During infection, RAGE functions to either exacerbate disease severity or enhance pathogen clearance depending on the pathogen studied. Acinetobacter baumannii is an opportunistic human pathogen capable of causing severe infections, including pneumonia and sepsis, in impaired hosts. The role of RAGE signaling in response to opportunistic bacterial infections is largely unknown. In murine models of A. baumannii pneumonia, RAGE signaling alters neither inflammation nor bacterial clearance. In contrast, RAGE Ϫ/Ϫ mice systemically infected with A. baumannii exhibit increased survival and reduced bacterial burdens in the liver and spleen. The increased survival of RAGE Ϫ/Ϫ mice is associated with increased circulating levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Neutralization of IL-10 in RAGE Ϫ/Ϫ mice results in decreased survival during systemic A. baumannii infection that mirrors that of wild-type (WT) mice, and exogenous IL-10 administration to WT mice enhances survival in this model. These findings demonstrate the role for RAGE-dependent IL-10 suppression as a key modulator of mortality from Gram-negative sepsis.KEYWORDS Acinetobacter baumannii, IL-10, innate immunity, pneumonia, RAGE, receptor for advanced glycation end products, sepsis A n effective immune response to an invading pathogen depends upon host recognition of the infecting organism and resultant initiation of an immune response. This process is accomplished through the recognition of pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) (1). Signaling downstream of PRRs, including Toll-like receptors (TLRs), activates transcription factors such as nuclear factor kappa B (NF-B), inducing expression of proinflammatory genes and thereby altering cytokine and chemokine production, resulting in inflammation and effector cell recruitment to the site of infection (1, 2). In addition to PAMPs, many PRRs have also evolved to detect altered host proteins, referred to as danger-associated molecular patterns (DAMPs) (3). The signaling mechanisms required to initiate an appropriate response to an invading pathogen may also potentiate inflammation during the course of infection, and this inflammatory response may enhance tissue damage and exacerbate disease (4). The maladaptive potentiation of inflammation in response to infection is responsible for many of the severe manifestations of infectious

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Section: Methodsmentioning

confidence: 99%

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

et al. 2017

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“…All animal experiments were approved by the Vanderbilt University Institutional Animal Care and Use Committee. The murine model of A. baumannii pneumonia was performed as previously described (31)(32)(33)(34)(35)(36). Briefly, A. baumannii ATCC 17978 bacteria were back diluted 1:1,000 from overnight culture and grown for 3.5 h at 37°C with shaking, washed twice with cold PBS, and resuspended in PBS at an appropriate cell density for infection.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were challenged intranasally with 3 ϫ 10 8 CFU A. baumannii and humanely euthanized at 36 h postinfection, as previously described (31). This time point was chosen because bacterial burdens and lung pathology peak in severity at approximately 36 h postinfection in this nonlethal pneumonia model (32). Compared to the lung burdens in wild-type mice, TLR9…”

Section: A Baumannii Activates Nf-b In a Tlr9-dependent Mannermentioning

confidence: 99%

Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection

et al. 2015

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dAcinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to A. baumannii infection. In a murine model of A. baumannii pneumonia, TLR9؊/؊ mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic A. baumannii infection, TLR9؊/؊ mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen Acinetobacter baumannii.

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“…Furthermore, CP is antimicrobial against several pathogens, including A. baumannii, in a manner dependent on its metal-chelating properties (15,(17)(18)(19)(20)(21)(22). Following A. baumannii pulmonary infection, CP is observed in the lungs of infected mice, and its abundance and distribution reflect the inflammatory response to infection (23). Importantly, CP is required for controlling A. baumannii pneumonia, as S100A9 Ϫ/Ϫ mice exhibit higher bacterial organ burdens than wild-type mice (18).…”

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Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

et al. 2014

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Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia in intensive care units, and the increasing rates of antibiotic resistance make treating these infections challenging. Consequently, there is an urgent need to develop new antimicrobials to treat A. baumannii infections. One potential therapeutic option is to target bacterial systems involved in maintaining appropriate metal homeostasis, processes that are critical for the growth of pathogens within the host. The A. baumannii inner membrane zinc transporter ZnuABC is required for growth under low-zinc conditions and for A. baumannii pathogenesis. The expression of znuABC is regulated by the transcriptional repressor Zur. To investigate the role of Zur during the A. baumannii response to zinc limitation, a zur deletion mutant was generated, and transcriptional changes were analyzed using RNA sequencing. A number of Zur-regulated genes were identified that exhibit increased expression both when zur is absent and under lowzinc conditions, and Zur binds to predicted Zur box sequences of several genes affected by zinc levels or the zur mutation. Furthermore, the zur mutant is impaired for growth in the presence of both high and low zinc levels compared to wild-type A. baumannii. Finally, the zur mutant exhibits a defect in dissemination in a mouse model of A. baumannii pneumonia, establishing zinc sensing as a critical process during A. baumannii infection. These results define Zur-regulated genes within A. baumannii and demonstrate a requirement for Zur in the A. baumannii response to the various zinc levels experienced within the vertebrate host.

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Imaging mass spectrometry for assessing temporal proteomics: Analysis of calprotectin in Acinetobacter baumannii pulmonary infection

Cited by 48 publications

References 52 publications

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection

Acinetobacter baumannii Response to Host-Mediated Zinc Limitation Requires the Transcriptional Regulator Zur

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