scholarly journals Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection.

1992 ◽  
Vol 36 (7) ◽  
pp. 1412-1417 ◽  
Author(s):  
E Vallee ◽  
E Azoulay-Dupuis ◽  
J J Pocidalo ◽  
E Bergogne-Berezin
2021 ◽  
Vol 12 ◽  
Author(s):  
Rabeb Dhouib ◽  
Marufa Nasreen ◽  
Dk Seti Maimonah Pg Othman ◽  
Daniel Ellis ◽  
Simon Lee ◽  
...  

Although molybdenum-containing enzymes are well-established as having a key role in bacterial respiration, it is increasingly recognized that some may also support bacterial virulence. Here, we show that DmsABC, a putative dimethylsulfoxide (DMSO) reductase, is required for fitness of the respiratory pathogen Haemophilus influenzae (Hi) in different models of infection. Expression of the dmsABC operon increased with decreasing oxygen availability, but despite this, a Hi2019ΔdmsA strain did not show any defects in anaerobic growth on chemically defined medium (CDM), and viability was also unaffected. Although Hi2019ΔdmsA exhibited increased biofilm formation in vitro and greater resistance to hypochlorite killing compared to the isogenic wild-type strain, its survival in contact with primary human neutrophils, in infections of cultured tissue cells, or in a mouse model of lung infection was reduced compared to Hi2019WT. The tissue cell infection model revealed a two-fold decrease in intracellular survival, while in the mouse model of lung infection Hi2019ΔdmsA was strongly attenuated and below detection levels at 48 h post-inoculation. While Hi2019WT was recovered in approximately equal numbers from bronchoalveolar lavage fluid (BALF) and lung tissue, survival of Hi2019ΔdmsA was reduced in lung tissue compared to BALF samples, indicating that Hi2019ΔdmsA had reduced access to or survival in the intracellular niche. Our data clearly indicate for the first time a role for DmsABC in H. influenzae infection and that the conditions under which DmsABC is required in this bacterium are closely linked to interactions with the host.


2018 ◽  
Vol 38 (8) ◽  
pp. 4651-4659 ◽  
Author(s):  
FENG-YUN J. HUANG ◽  
CHENG-CHIEN HUNG ◽  
CHIEN-WEN CHANG ◽  
JIUNN-HSING CHAO ◽  
BOR-TSUNG HSIEH

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095647
Author(s):  
Xing Hu ◽  
Yun Cai ◽  
Yuhang Wang ◽  
Rui Wang ◽  
Jin Wang ◽  
...  

Objective To establish a mouse model of bioluminescent Klebsiella pneumoniae-induced lung infection, under different infection states after pretreatment with various dosages of cyclophosphamide (CTX). Methods A K. pneumoniae strain carrying the luxCDABE operon was used to infect immunocompetent mice (intraperitoneal injection of saline at 4 days and 1 day prior to experimental lung infection) and immunodeficient mice (50 mg/kg CTX at 4 days and 50 mg/kg CTX at 1 day prior to lung infection; or 150 mg/kg CTX at 4 days and 100 mg/kg CTX at 1 day prior to lung infection). Disease progression was monitored in living mice using a bioluminescence imaging system. The bioluminescent images, bacterial loads in lungs, blood cytological changes and histopathology of lungs were analysed. Results K. pneumoniae-induced lung infection models were established in mice pretreated with CTX. Different doses of CTX led to different severities of lung infection. Mice pretreated with 150/100 mg/kg CTX were more suitable for real-time monitoring as they had more typical bioluminescent images of lung infection, more obvious changes in the bioluminescent intensity values, more bacterial colonies in the lungs and more distinct pulmonary pathological changes. Conclusions A stable bioluminescent K. pneumonia-induced lung infection model was successfully established in mice pretreated with CTX, which can be semi-quantitatively monitored in real-time.


Infection ◽  
1992 ◽  
Vol 20 (6) ◽  
pp. 360-364 ◽  
Author(s):  
P. H. Di Rocco ◽  
M. C. Nacucchio ◽  
F. Mancuso ◽  
D. O. Sordelli ◽  
Anne Morris Hooke
Keyword(s):  

2010 ◽  
Vol 59 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber

Acute lung injuries due to acute lung infections remain a major cause ofmortality. Thus a combination of an antibiotic and a compound with immunomodulatoryand anti-inflammatory activities can help to overcome acute lung infection-inducedinjuries. Curcumin derived from the rhizome of turmeric has been used fordecades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatoryproperties by downregulation of various inflammatory mediators. Keeping theseproperties in mind, we investigated the anti-inflammatory properties of curcuminin a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillationof bacteria in this mouse model of acute pneumonia-induced inflammation resultedin a significant increase in neutrophil infiltration in the lungs along withincreased production of various inflammatory mediators [i.e. malondialdehyde (MDA),myeloperoxidase (MPO), nitric oxide (NO), tumour necrosisfactor (TNF)-α] in the lung tissue. The animalsthat received curcumin alone orally or in combination with augmentin, 15 daysprior to bacterial instillation into the lungs via the intranasal route, showeda significant (P <0.05) decrease in neutrophil influxinto the lungs and a significant (P <0.05) decreasein the production of MDA, NO, MPO activity and TNF-α levels.Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-α levels significantly (P >0.05) as compared tothe control group. We therefore conclude that curcumin ameliorates lung inflammationinduced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereasaugmentin takes care of bacterial proliferation. Hence, curcumin can be usedas an adjunct therapy along with antibiotics as an anti-inflammatory or animmunomodulatory agent in the case of acute lung infection.


2011 ◽  
Vol 79 (8) ◽  
pp. 3366-3376 ◽  
Author(s):  
Charles V. Rosadini ◽  
Jeffrey D. Gawronski ◽  
Daniel Raimunda ◽  
José M. Argüello ◽  
Brian J. Akerley

ABSTRACTNontypeableHaemophilus influenzae(NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence ofH. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the “zinc bindingessential forvirulence” (zev) locus consisting ofzevA(HI1249) andzevB(HI1248). NTHI mutants ofzevAandzevBgrew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate thatzevABis a novel virulence factor important for zinc utilization ofH. influenzaeunder conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.


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