scholarly journals Chronic cigarette smoke exposure and pneumococcal infection induce oropharyngeal microbiota dysbiosis and contribute to long-lasting lung damage in mice

2020 ◽  
Vol 6 (12) ◽  
Author(s):  
Markus Hilty ◽  
Tsering M. Wüthrich ◽  
Aurélie Godel ◽  
Roberto Adelfio ◽  
Susanne Aebi ◽  
...  

Environmental factors, such as cigarette smoking or lung infections, may influence chronic obstructive pulmonary disease (COPD) progression by modifying the respiratory tract microbiome. However, whether the disease itself induces or maintains dysbiosis remains undefined. In this longitudinal study, we investigated the oropharyngeal microbiota composition and disease progression of mice (in cages of 5–10 mice per cage) before, during and up to 3 months after chronic cigarette smoke exposure or exposure to room air for 6 months. Cigarette smoke exposure induced pulmonary emphysema measurable at the end of exposure for 6 months, as well as 3 months following smoke exposure cessation. Using both classical culture methods and 16S rRNA sequencing, we observed that cigarette smoke exposure altered the relative composition of the oropharyngeal microbiota and reduced its diversity (P <0.001). More than 60 taxa were substantially reduced after 6 months of smoke exposure (P <0.001) However, oropharyngeal microbiota disordering was reversed 3 months after smoke exposure cessation and no significant difference was observed compared to age-matched control mice. The effects of lung infection with Streptococcus pneumoniae on established smoke-induced emphysema and on the oropharyngeal microbiota were also evaluated. Inoculation with S. pneumoniae induced lung damage and altered the microbiota composition for a longer time compared to control groups infected but not previously exposed to smoke (P=0.01). Our data demonstrate effects of cigarette smoke and pneumococcus infection leading to altered microbiota and emphysema development. The reversal of the disordering of the microbiota composition, but not lung damage, following smoke exposure cessation and after clearance of infection suggest that changes in lung structure are not sufficient to sustain a disordered microbiota in mice. Whether changes in the airway microbiota contribute to inducing emphysema requires further investigation.

2017 ◽  
Vol 85 (10) ◽  
Author(s):  
Pamela Shen ◽  
Fiona J. Whelan ◽  
L. Patrick Schenck ◽  
Joshua J. C. McGrath ◽  
Gilles Vanderstocken ◽  
...  

ABSTRACT Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization.


2020 ◽  
Vol 6 (12) ◽  
Author(s):  
Alexander Bolotin ◽  
Benoit Quinquis ◽  
Hugo Roume ◽  
Michel Gohar ◽  
Didier Lereclus ◽  
...  

Bacillus thuringiensis serovar israelensis is the most widely used natural biopesticide against mosquito larvae worldwide. Its lineage has been actively studied and a plasmid-free strain, B . thuringiensis serovar israelensis BGSC 4Q7 (4Q7), has been produced. Previous sequencing of the genome of this strain has revealed the persistent presence of a 235 kb extrachromosomal element, pBtic235, which has been shown to be an inducible prophage, although three putative chromosomal prophages have been lost. Moreover, a 492 kb region, potentially including the standard replication terminus, has also been deleted in the 4Q7 strain, indicating an absence of essential genes in this area. We reanalysed the genome coverage distribution of reads for the previously sequenced variant strain, and sequenced two independently maintained samples of the 4Q7 strain. A 553 kb area, close to the 492 kb deletion, was found to be duplicated. This duplication presumably restored the equal sizes of the replichores, and a balanced functioning of replication termination. An analysis of genome assembly graphs revealed a transient association of the host chromosome with the pBtic235 element. This association may play a functional role in the replication of the bacterial chromosome, and the termination of this process in particular. The genome-restructuring events detected may modify the genetic status of cytotoxic or haemolytic toxins, potentially influencing strain virulence. Twelve of the single-nucleotide variants identified in 4Q7 were probably due to the procedure used for strain construction or were present in the precursor of this strain. No sequence variants were found in pBtic235, but the distribution of the corresponding 4Q7 reads indicates a significant difference from counterparts in natural B. thuringiensis serovar israelensis strains, suggesting a duplication or over-replication in 4Q7. Thus, the 4Q7 strain is not a pure plasmid-less offshoot, but a highly genetically modified derivative of its natural ancestor. In addition to potentially influencing virulence, genome-restructuring events can modify the replication termination machinery. These findings have potential implications for the conclusions of virulence studies on 4Q7 as a model, but they also raise interesting fundamental questions about the functioning of the Bacillus genome.


2021 ◽  
Vol 70 (5) ◽  
Author(s):  
Weiping Wang ◽  
Jinghui Yang ◽  
Xiaocui Wu ◽  
Baoshan Wan ◽  
Hongxiu Wang ◽  
...  

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria. Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare . Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species ( Mycobacterium avium and Mycobacterium intracellulare ) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions. Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M . intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions. Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml−1) than M. intracellulare (8 µg ml−1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml−1) than M. avium (≤0.25 µg ml−1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections. Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.


2020 ◽  
Vol 8 (1) ◽  
pp. 45
Author(s):  
Alfreda Sabrina Widyanti ◽  
Martha Ardiaria ◽  
Nurmasari Widyastuti

Background: Cigarette smoke exposure is one of the source of free radicals that causes oxidative stress and decreases superoxide dismutase (SOD) level. Purple fleshed sweet potato is a type of food that contains antioxidants to neutralize oxidative stress.Objectives: To study the effect of purple fleshed sweet potato on superoxide dismutase (sod) level on rats exposed to cigarette smoke.Methods: This was a true experimental study with a post-test randomized control group design. The rats were randomized into 4 groups (6 rats in each group). The negative control group (K-) was treated with standard diet; the positive control group (K+) was treated with cigarette smoke exposure and standard diet; the treatment 1 (P1) group was treated with standard diet and purple fleshed sweet potato with the dose of 8 g / 200 g bw/day, and the treatment 2 (P2) group was treated with cigarette smoke exposure and purple fleshed sweet potato with the dose of 8 g /200 g bw/day.Results: There was a significant difference of SOD levels in each group (p=0.00) except between group K- and P1. Giving purple fleshed sweet potatoes increased SOD levels as much as 85.81±4.59 (P1). The K+ group had the lowest SOD level 22.34±3.98. The SOD level for K- group and P2 group was 82.27±4.59 and 67.73±6.68 respectively.Conclusion: The highest SOD level is on the treatment 1 group which is administered with purple fleshed sweet potato.


2020 ◽  
Vol 2 (12) ◽  
Author(s):  
Ameerah M. Alazemi ◽  
W. Jamal ◽  
A. Al Khabbaz ◽  
V. O. Rotimi

Introduction. Periodontal diseases are a group of chronic infections that destroy tissues surrounding and supporting the teeth. Data on the anaerobes associated with periodontal infections in Kuwait is lacking. Aim. To investigate the target anaerobes associated with chronic periodontitis (CP) in patients admitted to Dental Clinics in Kuwait University Health Sciences Center, Kuwait. Methodology. Patients with CP (severe and moderate) were recruited into this study during a period of 15 months. Samples were collected directly from inside the gingival pockets and subjected to semi-quantitative PCR assays. Results. A total of 30 patients, stratified into moderate and severe CP and 31 healthy individuals, used as controls, were studied. Nine (30 %) of the 30 patients were in the 50–59-year age group. The detection rate of Aggregatibacter actinomycetemcomitans between the patients (9 : 30 %) versus the controls (5 : 16.1 %) was non-significant (P >0.05). Fusobacterium spp., were detected in all patients versus 29 (93.1 %) controls, (P >0.05). However, four target anaerobes were significantly associated with CP patients; Porphyromonas gingivalis was detected in ten (33.3 %) patients versus two (6.4 %) controls (P <0.0001); Tannerella forsythia 25 (83.3 %) versus 16 (51.6 %) controls (P <0.0001); Parvimonas micra 27 (90 %) versus 16 (51.6 %) controls (P <0.0001) and Treponema denticola, 18 (60 %) versus nine (29 %) controls (P <0.0001), respectively. Prevotella spp. were detected in 27 (90 %) patients and 30 (96.7 %) controls (P>0.5). There was no significant difference in the burden of Prevotella spp. between patients and controls determined by semi-quantitative PCR assays. Conclusion. Some (4/7) of the target anaerobes were significantly associated with CP in our study. P. gingivalis was the most strongly associated anaerobe with CP, although not the keystone bacteria, while Prevotella spp. was similar to the healthy controls.


Author(s):  
Endy Novryan Ridwan ◽  
Martono Tri Utomo ◽  
Harianto Notopuro

Introduction: This research aims to investigate and observe the effect of cigarette smoke exposure in the fetal growth and fetal development of mice (Mus musculus).  Methods: This was an experiment with post-test only control group design. The sample of the research was 36 pregnant mice which were randomly divided into 2 groups: control group (K) pregnant mice which inhaled ambient air without cigarette smoke exposure, and treatment group (P) pregnant mice which were given cigarette smoke exposure for 14 days with 2 bars of cigarette each day.  Results: The results showed a significant difference in the fetal birth weight between the group exposed to cigarette smoke (p < 0.05) compared with the control group. Fetal defect and stillbirth were not found in this research. Conclusion: The exposure of cigarette smoke gave negative effects of fetal growth and development because of the free radicals generated.


2014 ◽  
Vol 307 (9) ◽  
pp. L718-L726 ◽  
Author(s):  
Sandra Pérez-Rial ◽  
Laura del Puerto-Nevado ◽  
Álvaro Girón-Martínez ◽  
Raúl Terrón-Expósito ◽  
Juan J. Díaz-Gil ◽  
...  

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD.


2016 ◽  
Vol 84 (5) ◽  
pp. 1536-1547 ◽  
Author(s):  
Pamela Shen ◽  
Mathieu C. Morissette ◽  
Gilles Vanderstocken ◽  
Yang Gao ◽  
Muhammad Hassan ◽  
...  

Streptococcus pneumoniaeis a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.


2021 ◽  
Vol 9 (A) ◽  
pp. 123-128
Author(s):  
Achmad Ramadhan

BACKGROUND: Cigarette smoke has a variety of dangerous chemicals and free radicals that can potentially cause infertility. One of the plants that are reported to have medicinal properties and have active compounds as antioxidants is Binahong (Anredera cordifolia (Ten.) Steenis). AIM: This study aims to investigate the effectiveness of A. cordifolia leaf extract (ACLE) in increasing the fertility of male Wistar rats after exposure to cigarette smoke. METHODS: Twenty-four adult male rats were divided into six groups (age 8–10 weeks, weight 200–250 g): Group 1 (normal control) received aquades (1 ml/day) without being given cigarette smoke, Group 2 received exposure to smoke without being given ACLE, Group 3 received cigarette smoke exposure + 25 mg/kg ACLE, Group 4 received cigarette smoke exposure + 50 mg/kg ACLE, Group 5 received cigarette smoke exposure + 75 mg/kg ACLE, and Group 6 received exposure to cigarette smoke + 100 mg/kg of ACLE. To produce smoke from cigarettes and expose rats to the smoke, a Smoke chamber is used. Rats in the treatment group were exposed to cigarette smoke for 2 weeks (40–60 s daily for 6 days each week). The evaluation of male rat fertility was carried out by measuring body weight, genital weight (testis and epididymis), and spermatozoa spermogram (velocity, motility, morphology, and total number). RESULTS: The least significance different test results showed no significant difference in the rate of weight gain between treatments, standard control, and negative control groups. The average testicular weight of rats exposed to cigarette smoke for 14 days was significantly different from normal controls and doses of 50, 75, and 100 mg/kg body weight. However, at a dose of 25 mg/kg of body weight had not shown a significant increase compared to control. The average spermatozoa velocity reached 12.43 mm2/s and 13.36 mm2/s. The spermatozoa velocity increased significantly at a dose of 100 mg/kg body weight. CONCLUSIONS: ACLE at a dose of 100 mg/kg body weight was effective in increasing the fertility of male Wistar rats exposed to cigarette smoke.


Author(s):  
Manlin Ding ◽  
Jiao Shi ◽  
Ahmad Ud Din ◽  
Yao Liu ◽  
Feiyang Zhang ◽  
...  

Introduction. Since mcr-1 was first reported in China, there have been ten variants of MCR appearing nationwide so far. Multidrug-resistant Enterobacteriaceae bacteria carrying both NDM and MCR have become a serious threat to global public health. Hypothesis/Gap Statement. The genetic structure of mcr-9 needs to be better understood in order to better prevent and control the transmission of drug-resistant genes. Aims. The aim of this study was to characterize the presence of two Enterobacter hormaechei isolates, which carries bla NDM-5 CME2 and the coexistence of mcr-9 and bla NDM-1 strain CMD2, which were isolated from a patient with diabetes in Sichuan, China. Methodology. The microbroth dilution method was used for antibiotic susceptibility. Conjugation experiment was used to investigate the transferability of bla NDM-1, bla NDM-5 and mcr-9. Whole-genome sequencing was performed on Illumina HiSeq platform. The ability of biofilm formation was detected by crystal-violet staining, the virulence of the bacteria was measured by Galleria mellonella killing assay. Results. bla NDM-5 carrier CME2 and CMD2 with bla NDM-1 and mcr-9 were resistant to carbapenems, β-lactam, aminoglycoside, quinolone and tetracycline, while CMD2 was also resistant to colistin. Conjugation assay and plasmid replicon typing further demonstrated that both bla NDM-1 and bla NDM-5 were respectively present on the self-transferrable IncX3 plasmid, mcr-9 was located on the self-transferrable IncHI2 plasmid. Through the analysis of mcr-9 gene context, the structure was DUF4942-rcnR-rcnA-copS-IS903-mcr-9-wbuC-qseC-qseB-IS1R-ΔsilR-IS903, bla NDM-1 context was IS3000-ΔISAba125-IS5-bla NDM-1-ble-trpF-groS-groL-insE-ΔIS26 structure, bla NDM-5 structure was IS3000-bla NDM-5-ble-trpF-dsbC-ΔIS26-umuD-ISKox3-tnpR-parA. Biofilm formation of CME2 was stronger than CMD2. There was no significant difference in virulence between the two strains. Conclusion. This study reveals two multiple drug-resistant E. hormaechei isolates from diabetes patient samples. E. hormaechei carrying two NDM-resistant genes is already a serious threat, where MCR is an important cause of treatment failure in bacterial infections. This study is a reminder not only to prevent infection in patients with diabetes, but also to constantly monitor the epidemic and spread of the drug-resistant gene.


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