scholarly journals Genomic diversity and antimicrobial resistance of Haemophilus colonising the airways of young children with cystic fibrosis

2020 ◽  
Author(s):  
Stephen C. Watts ◽  
Louise M. Judd ◽  
Rosemary Carzino ◽  
Sarath Ranganathan ◽  
Kathryn E. Holt

AbstractRespiratory infection during childhood is a key risk factor in early cystic fibrosis (CF) lung disease progression. Haemophilus influenzae (Hi) and Haemophilus parainfluenzae (Hpi) are routinely isolated from the lungs of children with CF, however little is known about the frequency and characteristics of Haemophilus colonisation in this context. Here, we describe detection, antimicrobial resistance (AMR) and genome sequencing of Hi/Hpi isolated from sputum, cough swab, and bronchoalveolar lavage samples regularly collected from 147 participants aged ≤12 years enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program. The frequency of colonisation per visit was 4.6% for Hi and 32.1% for Hpi, 80.3% of participants had Hi and/or Hpi detected on at least one visit, and using genomic data we estimate 15.6% of participants had persistent colonisation with the same strain for at least two consecutive visits. Colonising strains were genetically highly diverse and AMR was common, with 52% of Hi and 82% of Hpi displaying resistance to at least one drug. The genetic basis for AMR could be identified in most cases; novel determinants include a new plasmid encoding blaTEM-1 (ampicillin resistance), a new inhibitor-resistant blaTEM allele (augmentin resistance), and previously unreported mutations in chromosomally-encoded genes (pbp3, ampicillin resistance; folA and folP, co-trimoxazole resistance; rpoB, rifampicin resistance). Acquired AMR genes were significantly more common in Hpi than Hi (51% vs 21%, p=0.0107) and were mostly associated with the ICEHin mobile element carrying blaTEM-1, resulting in higher rates of ampicillin resistance in Hpi (73% vs 30%, p=0.0004). The genome data identified six potential instances of Haemophilus transmission between participants, three of which involved participant pairs who attended the clinic on the same day. The high prevalence of Haemophilus colonisation and high burden of antimicrobial use in children with CF likely provides a reservoir for emergence and spread of AMR as well as a source of infections.

mSystems ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Stephen C. Watts ◽  
Louise M. Judd ◽  
Rosemary Carzino ◽  
Sarath Ranganathan ◽  
Kathryn E. Holt

Cystic fibrosis (CF) lung disease begins during infancy, and acute respiratory infections increase the risk of early disease development and progression. Microbes involved in advanced stages of CF are well characterized, but less is known about early respiratory colonizers.


2020 ◽  
Author(s):  
Ruben Monarrez ◽  
Iruka Okeke

Abstract Objective: Plasmids are key to antimicrobial resistance transmission among enteric bacteria. It is becoming increasingly clear that resistance genes alone do not account for the selective advantage of plasmids and bacterial strains that harbor them. Deletion of a 32 Kb fitness-conferring region of pMB2, a conjugative resistance plasmid, produced a hyper-autoaggregation phenotype in laboratory Escherichia coli. This study sought to determine the genetic basis for hyper-autoaggregation conferred by the pMB2-derived mini-plasmid. Results: The 32 Kb fragment deleted from pMB2 included previously characterized nutrient acquisition genes as well as putative transposase and integrase genes, a 272 bp papB/ pefB-like gene, and several open-reading frames of unknown function. We cloned the papB/ pefB paralogue and found it sufficient to temper the hyper-autoaggregation phenotype. Hyper-autoaggregation conferred by the mini-plasmid did not occur in a fim-negative background. This study has identified and characterized a gene capable of down-regulating host adhesins and has shown that trans-acting papB/pefB paralogues can occur outside the context of an adhesin cluster. This plasmid-mediated modification of a bacterial host’s colonization program may optimize horizontal transfer of the mobile element bearing the genes.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Rubén Monárrez ◽  
Iruka N. Okeke

Abstract Objective Plasmids are key to antimicrobial resistance transmission among enteric bacteria. It is becoming increasingly clear that resistance genes alone do not account for the selective advantage of plasmids and bacterial strains that harbor them. Deletion of a 32 Kb fitness-conferring region of pMB2, a conjugative resistance plasmid, produced a hyper-autoaggregation phenotype in laboratory Escherichia coli. This study sought to determine the genetic basis for hyper-autoaggregation conferred by the pMB2-derived mini-plasmid. Results The 32 Kb fragment deleted from pMB2 included previously characterized nutrient acquisition genes as well as putative transposase and integrase genes, a 272 bp papB/ pefB-like gene, and several open-reading frames of unknown function. We cloned the papB/ pefB paralogue and found it sufficient to temper the hyper-autoaggregation phenotype. Hyper-autoaggregation conferred by the mini-plasmid did not occur in a fim-negative background. This study has identified and characterized a gene capable of down-regulating host adhesins and has shown that trans-acting papB/pefB paralogues can occur outside the context of an adhesin cluster. This plasmid-mediated modification of a bacterial host’s colonization program may optimize horizontal transfer of the mobile element bearing the genes.


2016 ◽  
Vol 55 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Chloé Dupont ◽  
Estelle Jumas-Bilak ◽  
Anne-Laure Michon ◽  
Raphaël Chiron ◽  
Hélène Marchandin

ABSTRACT Chronic colonization by opportunistic environmental bacteria is frequent in the airways of cystic fibrosis (CF) patients. Studies of Pseudomonas aeruginosa evolution during persistence have highlighted the emergence of pathoadaptive genotypes and phenotypes, leading to complex and diversified inpatient colonizing populations also observed at the intraspecimen level. Such diversity, including heterogeneity in resistance profiles, has been considered an adaptive strategy devoted to host persistence. Longitudinal genomic diversity has been shown for the emergent opportunistic pathogen Achromobacter , but phenotypic and genomic diversity has not yet been studied within a simple CF sputum sample. Here, we studied the genomic diversity and antimicrobial resistance heterogeneity of 132 Achromobacter species strains (8 to 27 strains of identical or distinct colonial morphotypes per specimen) recovered from the sputum samples of 9 chronically colonized CF patients. We highlighted the high within-sample and within-morphotype diversity of antimicrobial resistance (disk diffusion) and genomic (pulsed-field gel electrophoresis) profiles. No sputum sample included strains with identical pulsotypes or antibiotic susceptibility patterns. Differences in clinical categorization were observed for the 9 patients and concerned 3 to 11 antibiotics, including antibiotics recommended for use against Achromobacter . Within-sample antimicrobial resistance heterogeneity, not predictable from colonial morphology, suggested that it may represent a selective advantage against antibiotics in an Achromobacter persisting population and potentially compromise the antibiotic management of CF airway infections.


2020 ◽  
Author(s):  
Ruben Monarrez ◽  
Iruka Okeke

Abstract Objective: Plasmids are key to antimicrobial resistance transmission among enteric bacteria. It is becoming increasingly clear that resistance genes alone do not account for the selective advantage of plasmids and bacterial strains that harbor them. Deletion of a 32 Kb fitness-conferring region of pMB2, a conjugative resistance plasmid, produced a hyper-autoaggregation phenotype in laboratory Escherichia coli. This study sought to determine the genetic basis for hyper-autoaggregation conferred by the pMB2-derived mini-plasmid. Results: The 32 Kb fragment deleted from pMB2 included previously characterized nutrient acquisition genes as well as putative transposase and integrase genes, a 272 bp papB/ pefB-like gene, and several open-reading frames of unknown function. We cloned the papB/ pefB paralogue and found it sufficient to temper the hyper-autoaggregation phenotype. Hyper-autoaggregation conferred by the mini-plasmid did not occur in a fim-negative background. This study has identified and characterized a gene capable of down-regulating host adhesins and has shown that trans-acting papB/pefB paralogues can occur outside the context of an adhesin cluster. This plasmid-mediated modification of a bacterial host’s colonization program may optimize horizontal transfer of the mobile element bearing the genes.


2020 ◽  
Author(s):  
Ruben Monarrez ◽  
Iruka Okeke

Abstract Objective: Plasmids are key to the transmission of antimicrobial resistance among enteric bacteria. It is becoming increasingly clear that resistance genes alone do not account for the selective advantage of plasmids and bacterial strains that harbor them. Deletion of a 32 Kb fitness-conferring region of pMB2, a conjugative resistance plasmid, produced a hyper­autoaggregation phenotype in laboratory Escherichia coli. This study sought to determine the genetic basis for hyper-autoaggregation conferred by the pMB2-derived mini-plasmid.Results: The 32 Kb fragment deleted from pMB2 included previously characterized nutrient acquisition genes as well as putative transposase and integrase genes, a 272 bp papB/ pefB-like gene, and several open-reading frames of unknown function. We cloned the papB/ pefB paralogue and found it sufficient to temper the hyper-autoaggregation phenotype. Hyper­autoaggregation conferred by the mini-plasmid did not occur in a fim-negative background. This study has identified and characterized a gene capable of down-regulating host adhesins and has shown that trans-acting papB/pefB paralogues can occur outside the context of an adhesin cluster. This plasmid-mediated modification of a bacterial host’s colonization program may optimize horizontal transfer of the mobile element bearing the genes.


2020 ◽  
Vol 26 (24) ◽  
pp. 2807-2816 ◽  
Author(s):  
Yun Su Jang ◽  
Tímea Mosolygó

: Bacteria within biofilms are more resistant to antibiotics and chemical agents than planktonic bacteria in suspension. Treatment of biofilm-associated infections inevitably involves high dosages and prolonged courses of antimicrobial agents; therefore, there is a potential risk of the development of antimicrobial resistance (AMR). Due to the high prevalence of AMR and its association with biofilm formation, investigation of more effective anti-biofilm agents is required. : From ancient times, herbs and spices have been used to preserve foods, and their antimicrobial, anti-biofilm and anti-quorum sensing properties are well known. Moreover, phytochemicals exert their anti-biofilm properties at sub-inhibitory concentrations without providing the opportunity for the emergence of resistant bacteria or harming the host microbiota. : With increasing scientific attention to natural phytotherapeutic agents, numerous experimental investigations have been conducted in recent years. The present paper aims to review the articles published in the last decade in order to summarize a) our current understanding of AMR in correlation with biofilm formation and b) the evidence of phytotherapeutic agents against bacterial biofilms and their mechanisms of action. The main focus has been put on herbal anti-biofilm compounds tested to date in association with Staphylococcus aureus, Pseudomonas aeruginosa and food-borne pathogens (Salmonella spp., Campylobacter spp., Listeria monocytogenes and Escherichia coli).


2020 ◽  
Vol 19 (3) ◽  
pp. 370-375 ◽  
Author(s):  
Edith Zemanick ◽  
Pierre–Régis Burgel ◽  
Giovanni Taccetti ◽  
Alison Holmes ◽  
Felix Ratjen ◽  
...  

2021 ◽  
Vol 8 (6) ◽  
pp. 111
Author(s):  
Md. Abul Kalam ◽  
Md. Abdul Alim ◽  
Shahanaj Shano ◽  
Md. Raihan Khan Nayem ◽  
Md. Rahim Badsha ◽  
...  

Poultry production has boomed in Bangladesh in recent years. The poultry sector has contributed significantly to meet the increased demand for animal source proteins in the country. However, increased use of antimicrobials and antibiotics appeared to be a significant threat to food safety in the poultry sector. The poultry drug and feed sellers are at the frontline position involving selecting and delivering the antimicrobials to the poultry farmers. Studies assessing the poultry drug and feed sellers’ knowledge, attitudes, and practices (KAPs) are limited. The current study aimed to assess the community poultry drug and feed sellers’ KAPs of antimicrobial use (AMU) and antimicrobial resistance (AMR) in some selected areas of Bangladesh. We determined the respondents’ (drug and the feed sellers) KAPs of AMU and AMR using a tested and paper-based questionnaire. The study demonstrated that most respondents have insufficient knowledge, less positive attitudes, and inappropriate practices regarding AMU and AMR. The factor score analysis further showed that the type of respondents and their years of experience, level of education, and training on the drug were the significant factors impacting the current knowledge, attitudes, and practices of AMU and AMR. The adjusted logistic regression analysis revealed that the drug sellers who completed their education up to 12th grade and had training on the drug had adequate knowledge of AMU and AMR. The data also showed that the drug sellers belong to the age group 31–35 and 36–40 years and who completed 12th grade had good attitudes on the same. Likewise, the analysis further determined that drug sellers belonging the age category 18–25 and 26–30 years, and interestingly, the respondents who completed education up to 12th grade, had better practices. Spearman’s rank-order correlation revealed a positive association between each pair of the KAPs scores for the respondents. The correlation was fair between knowledge–attitudes, knowledge–practices, and attitudes–practices. Based on the current study results, we recommend educational interventions and appropriate training for the poultry drug and feed sellers to raise awareness and to upgrade their current knowledge on the appropriate use of antimicrobials. This will ultimately lead to reducing the chances of developing AMR in the poultry sectors of the country.


2006 ◽  
Vol 27 (10) ◽  
pp. 1088-1095 ◽  
Author(s):  
Alan J. Zillich ◽  
Jason M. Sutherland ◽  
Stephen J. Wilson ◽  
Daniel J. Diekema ◽  
Erika J. Ernst ◽  
...  

Objective.Clinical practice guidelines and recommended practices to control use of antibiotics have been published, but the effect of these practices on antimicrobial resistance (AMR) rates in hospitals is unknown. The objective of this study was to examine relationships between antimicrobial use control strategies and AMR rates in a national sample of US hospitals.Design.Cross-sectional, stratified study of a nationally representative sample of US hospitals.Methods.A survey instrument was sent to the person responsible for infection control at a sample of 670 US hospitals. The outcome was current prevalences of 4 epidemiologically important, drug-resistant pathogens, considered concurrently: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, ceftazidime-resistant Klebsiella species, and quinolone (ciprofloxacin)-resistant Escherichia coli Five independent variables regarding hospital practices were selected from the survey: the extent to which hospitals (1) implement practices recommended in clinical practice guidelines and ensure best practices for antimicrobial use, (2) disseminate information on clinical practice guidelines for antimicrobial use, (3) use antimicrobial-related information technology, (4) use decision support tools, and (5) communicate to prescribers about antimicrobial use. Control variables included the hospitals' number of beds, teaching status, Veterans Affairs status, geographic region, and number of long-term care beds; and the presence of an intensive care unit, a burn unit, or transplant services. A generalized estimating equation modeled all resistance rates simultaneously to identify overall predictors of AMR levels at the facility.Results.Completed survey instruments were returned by 448 hospitals (67%). Four antimicrobial control measures were associated with higher prevalence of AMR. Implementation of recommended practices for antimicrobial use (P< .01) and optimization of the duration of empirical antibiotic prophylaxis (P<.01) were associated with a lower prevalence of AMR. Use of restrictive formularies (P = .05) and dissemination of clinical practice guideline information (P<.01) were associated with higher prevalence of AMR. Number of beds and Veterans Affairs status were also associated with higher AMR rates overall.Conclusions.Implementation of guideline-recommended practices to control antimicrobial use and optimize the duration of empirical therapy appears to help control AMR rates in US hospitals. A longitudinal study would confirm the results of this cross-sectional study. These results highlight the need for systems interventions and reengineering to ensure more-consistent application of guideline-recommended measures for antimicrobial use.


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