scholarly journals What is the role of the environment in the emergence of novel antibiotic resistance genes? – A modelling approach

2021 ◽  
Author(s):  
Johan Bengtsson-Palme ◽  
Viktor Jonsson ◽  
Stefanie Heß

AbstractIt is generally accepted that intervention strategies to curb antibiotic resistance cannot solely focus on human and veterinary medicine but must also consider environmental settings. While the environment clearly has a role in the transmission of resistant bacteria, it is less clear what role it plays in the emergence of novel types of resistance. It has been suggested that the environment constitutes an enormous recruitment ground for resistance genes to pathogens, but the extent to which this actually happens is unknown. In this study, we built a model framework for resistance emergence and used the available quantitative data on the relevant processes to identify the steps which are limiting the appearance of antibiotic resistance determinants in human or animal pathogens. We also assessed the effect of uncertainty in the available data on the model results. We found that in a majority of scenarios, the environment would only play a minor role in the emergence of novel resistance genes. However, the uncertainty around this role is enormous, highlighting an urgent need of more quantitative data to understand the role of the environment in antibiotic resistance development. Specifically, more data is most needed on the fitness costs of antibiotic resistance gene (ARG) carriage, the degree of dispersal of resistant bacteria from the environment to humans, but also the rates of mobilization and horizontal transfer of ARGs. Quantitative data on these processes is instrumental to determine which processes that should be targeted for interventions to curb development and transmission of resistance.

2011 ◽  
Vol 60 (2) ◽  
pp. 211-215 ◽  
Author(s):  
B. S. Lopes ◽  
A. Hamouda ◽  
J. Findlay ◽  
S. G. B. Amyes

Acinetobacter baumannii is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence ISAba1 in clinical isolates of A. baumannii, with the focus on changes in expression levels of the bla ADC and bla OXA-51-like genes. Resistance profiles were assessed with consideration of ISAba1 acting as a promoter upstream of the bla ADC or bla OXA-51-like gene. ISAba1 movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with ISAba1 gained upstream of the bla ADC and bla OXA-51-like genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of ISAba1 upstream of the bla ADC and bla OXA-51-like genes in strain Ab1225M, and a significant decrease in bla OXA-51-like gene expression and, to a lesser extent, in bla ADC expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had ISAba1 upstream of the bla ADC and bla OXA-51-like genes. A significant decrease in bla OXA-51-like expression was observed in Ab1225s, whereas the expression of bla ADC was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if ISAba1 is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes (bla OXA-51-like in Ab1225s). Movement of the IS element within the A. baumannii chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.


2016 ◽  
Vol 62 (2) ◽  
pp. 353-359 ◽  
Author(s):  
G Terrance Walker ◽  
Tony J Rockweiler ◽  
Rossio K Kersey ◽  
Kelly L Frye ◽  
Susan R Mitchner ◽  
...  

Abstract BACKGROUND Multiantibiotic-resistant bacteria pose a threat to patients and place an economic burden on health care systems. Carbapenem-resistant bacilli and extended-spectrum β-lactamase (ESBL) producers drive the need to screen infected and colonized patients for patient management and infection control. METHODS We describe a multiplex microfluidic PCR test for perianal swab samples (Acuitas® MDRO Gene Test, OpGen) that detects the vancomycin-resistance gene vanA plus hundreds of gene subtypes from the carbapenemase and ESBL families Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-mediated metallo-β-lactamase (VIM), imipenemase metallo-β-lactamase (IMP), OXA-23, OXA-48, OXA-51, CTX-M-1, and CTX-M-2, regardless of the bacterial species harboring the antibiotic resistance. RESULTS Analytical test sensitivity per perianal swab is 11–250 CFU of bacteria harboring the antibiotic resistance genes. Test throughput is 182 samples per test run (1820 antibiotic resistance gene family results). We demonstrate reproducible test performance and 100% gene specificity for 265 clinical bacterial organisms harboring a variety of antibiotic resistance genes. CONCLUSIONS The Acuitas MDRO Gene Test is a sensitive, specific, and high-throughput test to screen colonized patients and diagnose infections for several antibiotic resistance genes directly from perianal swab samples, regardless of the bacterial species harboring the resistance genes.


2019 ◽  
Vol 374 (1772) ◽  
pp. 20180384 ◽  
Author(s):  
Saadlee Shehreen ◽  
Te-yuan Chyou ◽  
Peter C. Fineran ◽  
Chris M. Brown

CRISPR-Cas systems are widespread in bacterial and archaeal genomes, and in their canonical role in phage defence they confer a fitness advantage. However, CRISPR-Cas may also hinder the uptake of potentially beneficial genes. This is particularly true under antibiotic selection, where preventing the uptake of antibiotic resistance genes could be detrimental. Newly discovered features within these evolutionary dynamics are anti-CRISPR genes, which inhibit specific CRISPR-Cas systems. We hypothesized that selection for antibiotic resistance might have resulted in an accumulation of anti-CRISPR genes in genomes that harbour CRISPR-Cas systems and horizontally acquired antibiotic resistance genes. To assess that question, we analysed correlations between the CRISPR-Cas, anti-CRISPR and antibiotic resistance gene content of 104 947 reference genomes, including 5677 different species. In most species, the presence of CRISPR-Cas systems did not correlate with the presence of antibiotic resistance genes. However, in some clinically important species, we observed either a positive or negative correlation of CRISPR-Cas with antibiotic resistance genes. Anti-CRISPR genes were common enough in four species to be analysed. In Pseudomonas aeruginosa , the presence of anti-CRISPRs was associated with antibiotic resistance genes. This analysis indicates that the role of CRISPR-Cas and anti-CRISPRs in the spread of antibiotic resistance is likely to be very different in particular pathogenic species and clinical environments. This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ana Belén Flórez ◽  
Ángel Alegría ◽  
Franca Rossi ◽  
Susana Delgado ◽  
Giovanna E. Felis ◽  
...  

Large antibiotic resistance gene pools in the microbiota of foods may ultimately pose a risk for human health. This study reports the identification and quantification of tetracycline- and erythromycin-resistant populations, resistance genes, and gene diversity in traditional Spanish and Italian cheeses, via culturing, conventional PCR, real-time quantitative PCR (qPCR), and denaturing gradient gel electrophoresis (DGGE). The numbers of resistant bacteria varied widely among the antibiotics and the different cheese varieties; in some cheeses, all the bacterial populations seemed to be resistant. Up to eight antibiotic resistance genes were sought by gene-specific PCR, six with respect to tetracycline, that is,tet(K),tet(L),tet(M),tet(O),tet(S), andtet(W), and two with respect to erythromycin, that is,erm(B) anderm(F). The most common resistance genes in the analysed cheeses weretet(S),tet(W),tet(M), anderm(B). The copy numbers of these genes, as quantified by qPCR, ranged widely between cheeses (from 4.94 to10.18log⁡10/g). DGGE analysis revealed distinct banding profiles and two polymorphic nucleotide positions fortet(W)-carrying cheeses, though the similarity of the sequences suggests thistet(W) to have a monophyletic origin. Traditional cheeses would therefore appear to act as reservoirs for large numbers of many types of antibiotic resistance determinants.


Author(s):  
Célia P. F. Domingues ◽  
João S. Rebelo ◽  
Teresa Nogueira ◽  
Joël Pothier ◽  
Francisca Monteiro ◽  
...  

1.AbstractThis study aims to understand the cause of the recent observation that humans with a higher diversity of virulence genes in their metagenomes tend to be precisely those with higher diversity of antibiotic-resistance genes. We simulated the transferring of virulence and antibiotic-resistance genes in a community of interacting people where some take antibiotics. The diversities of the two genes types became positively correlated whenever the contagion probability between two people was higher than the probability of losing resistant genes. However, no such positive correlations arise if no one takes antibiotics. This finding holds even under changes of several simulations’ parameters, such as the relative or total diversity of virulence and resistance genes, the contagion probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the contagion between people and antibiotic usage is the leading cause of establishing the positive correlation mentioned above. Therefore, antibiotic use and something as prosaic as the contagion between people may facilitate the emergence of virulent and multi-resistant bacteria in people’s metagenomes with a high diversity of both gene types. These superbugs may then circulate in the community.


mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Christopher J. Harmer ◽  
Robert A. Moran ◽  
Ruth M. Hall

ABSTRACTThe insertion sequence IS26plays a key role in disseminating antibiotic resistance genes in Gram-negative bacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26movement that explains the structure of these regions involves a translocatable unit consisting of a unique DNA segment carrying an antibiotic resistance (or other) gene and a single IS copy. Structures resembling class I transposons are generated via RecA-independent incorporation of a translocatable unit next to a second IS26such that the ISs are in direct orientation. Repeating this process would lead to arrays of resistance genes with directly oriented copies of IS26at each end and between each unique segment. This model requires that IS26recognizes another IS26as a target, and in transposition experiments, the frequency of cointegrate formation was 60-fold higher when the target plasmid contained IS26. This reaction was conservative, with no additional IS26or target site duplication generated, and orientation specific as the IS26s in the cointegrates were always in the same orientation. Consequently, the cointegrates were identical to those formed via the known mode of IS26movement when a target IS26was not present. Intact transposase genes in both IS26s were required for high-frequency cointegrate formation as inactivation of either one reduced the frequency 30-fold. However, the IS26target specificity was retained. Conversion of each residue in the DDE motif of the Tnp26 transposase also reduced the cointegration frequency.IMPORTANCEResistance to antibiotics belonging to several of the different classes used to treat infections is a critical problem. Multiply antibiotic-resistant bacteria usually carry large regions containing several antibiotic resistance genes, and in Gram-negative bacteria, IS26is often seen in these clusters. A model to explain the unusual structure of regions containing multiple IS26copies, each associated with a resistance gene, was not available, and the mechanism of their formation was unexplored. IS26-flanked structures deceptively resemble class I transposons, but this work reveals that the features of IS26movement do not resemble those of the IS and class I transposons studied to date. IS26uses a novel movement mechanism that defines a new family of mobile genetic elements that we have called “translocatable units.” The IS26mechanism also explains the properties of IS257(IS431) and IS1216, which belong to the same IS family and mobilize resistance genes in Gram-positive staphylococci and enterococci.


2018 ◽  
Author(s):  
Vanessa R. Marcelino ◽  
Michelle Wille ◽  
Aeron C. Hurt ◽  
Daniel González-Acuña ◽  
Marcel Klaassen ◽  
...  

AbstractAntibiotic resistance is rendering common bacterial infections untreatable. Wildlife can incorporate and disperse antibiotic resistant bacteria in the environment, such as water systems, which in turn serve as reservoirs of resistance genes for human pathogens. We used bulk RNA-sequencing (meta-transcriptomics) to assess the diversity and expression levels of functionally active resistance genes in the microbiome of birds with aquatic behavior. We sampled birds across a range of habitats, from penguins in Antarctica to ducks in a wastewater treatment plant in Australia. This revealed 81 antibiotic resistance genes in birds from all localities, including β-lactam, tetracycline and chloramphenicol resistance in Antarctica, and genes typically associated with multidrug resistance plasmids in areas with high human impact. Notably, birds feeding at a wastewater treatment plant carried the greatest resistance gene burden, suggesting that human waste, even if it undergoes treatment, contributes to the spread of antibiotic resistance genes to the wild. Differences in resistance gene burden also reflected the birds’ ecology, taxonomic group and microbial functioning. Ducks, which feed by dabbling, carried a higher abundance and diversity of resistance genes than turnstones, avocets and penguins, that usually prey on more pristine waters. In sum, this study helps to reveal the complex factors explaining the distribution of resistance genes and their exchange routes between humans and wildlife.


2016 ◽  
Vol 10 (08) ◽  
pp. 799-806 ◽  
Author(s):  
Raoudha Dziri ◽  
Carmen Lozano ◽  
Leila Ben Said ◽  
Ridha Bellaaj ◽  
Abdellatif Boudabous ◽  
...  

Introduction: The role of the hospital environment as a reservoir of resistant bacteria in Tunisia has been poorly investigated; however, it could be responsible for the transmission of multidrug-resistant bacteria. The objective was to study the prevalence of Enterococcus in the environment of a Tunisian hospital and the antibiotic resistance phenotype/genotype in recovered isolates, with special reference to vancomycin resistance. Methodology: A total of 300 samples were taken (March–June, 2013) and inoculated in Slanetz-Bartley agar plates supplemented or not supplemented with 8 µg/mL of vancomycin. Antibiotic resistance genes were tested by polymerase chain reaction (PCR). The clonal relatedness of the vanA isolates was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence testing (MLST). Results: Enterococci were recovered in 33.3% of tested samples inoculated in SB medium. E faecium was the most prevalent species, followed by E. faecalis and E. casseliflavus. Antimicrobial resistance genes detected were as follows (number of isolates): erm(B) (71), tet(M) (18), aph(3’)-IIIa (27), ant(6)-Ia (15), cat(A) (4), and van(C2) (6). Vancomycin-resistant-enterococci (VRE) were recovered from 14 samples (4.7%), when tested in SB-VAN. The 14 VRE (one per positive sample) were identified as E. faecium and contained the van(A),erm(B), tet(M), ant(6)-Ia, and aph(3’)-IIIa genes. Thirteen of the VRE strains were ascribed by PFGE and MLST to a novel clone (new ST910), and only one VRE strain was typed as ST80 included in CC17. Conclusions: The emergence and spread of new clones of VRE, especially in the hospital environment in this country, could become particularly problematic.


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