scholarly journals Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in Haemophilus influenzae

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Kristin Hegstad ◽  
Haima Mylvaganam ◽  
Jessin Janice ◽  
Ellen Josefsen ◽  
Audun Sivertsen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Haemophilus Influenzae ◽  
Resistance Genes ◽  
Mobile Genetic Elements ◽  
Beta Lactam ◽  
Content Type ◽  
Genetic Elements ◽  
Wide Range ◽  
Chromosomal Genes

ABSTRACT Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in H. influenzae is rare in Europe. In this study, we defined acquired resistance gene loci and ftsI mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) H. influenzae strains, intending to understand the mode of spread of antibiotic resistance determinants in this species. Horizontal transfer of mobile genetic elements and transformation with resistance-conferring ftsI alleles were contributory. We found one small plasmid and three novel integrative conjugative elements (ICEs) which carry different combinations of resistance genes. Demonstration of transfer and/or ICE circular forms showed that the ICEs are functional. Two extensively MDR genetically unrelated H. influenzae strains (F and G) from the same geographical region shared an identical novel MDR ICE (Tn6686) harboring blaTEM-1, catA2-like, and tet(B). The first Nordic case of MDR H. influenzae septicemia, strain 0, originating from the same geographical area as these strains, had a similar resistance pattern but contained another ICE [Tn6687 with blaTEM-1, catP and tet(B)] with an overall structure quite similar to that of Tn6686. Comparison of the complete ftsI genes among rPBP3 strains revealed that the entire gene or certain regions of it are identical in genetically unrelated strains, indicating horizontal gene transfer. Our findings illustrate that H. influenzae is capable of acquiring resistance against a wide range of commonly used antibiotics through horizontal gene transfer, in terms of conjugative transfer of ICEs and transformation of chromosomal genes. IMPORTANCE Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. As a threat to treatment, resistance against critically important antibiotics is on the rise in H. influenzae. Identifying mechanisms for horizontal acquisition of resistance genes is important to understand how multidrug resistance develops. The present study explores the antimicrobial resistance genes and their context in beta-lactam-resistant H. influenzae with coresistance to up to four non-beta-lactam groups. The results reveal that this organism is capable of acquiring resistance to a wide range of commonly used antibiotics through conjugative transfer of mobile genetic elements and transformation of chromosomal genes, resulting in mosaic genes with a broader resistance spectrum. Strains with chromosomally mediated resistance to extended-spectrum cephalosporins, co-trimoxazole, and quinolones combined with mobile genetic elements carrying genes mediating resistance to ampicillin, tetracyclines, and chloramphenicol have been reported, and further dissemination of such strains represents a particular concern.

scholarly journals CRISPR-Cas is associated with fewer antibiotic resistance genes in bacterial pathogens

2021 ◽  
Author(s):  
Elizabeth Pursey ◽  
Tatiana Dimitriu ◽  
Fernanda L. Paganelli ◽  
Edze R. Westra ◽  
Stineke van Houte
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Bacterial Pathogens ◽  
Genetic Material ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Defence System

AbstractThe acquisition of antibiotic resistance genes via horizontal gene transfer is a key driver of the rise in multidrug resistance amongst bacterial pathogens. Bacterial defence systems per definition restrict the influx of foreign genetic material, and may therefore limit the acquisition of antibiotic resistance. CRISPR-Cas adaptive immune systems are one of the most prevalent defences in bacteria, found in roughly half of bacterial genomes, but it has remained unclear if and how much they contribute to restricting the spread of antibiotic resistance. We analysed ~40,000 whole genomes comprising the full RefSeq dataset for 11 species of clinically important genera of human pathogens including Enterococcus, Staphylococcus, Acinetobacter and Pseudomonas. We modelled the association between CRISPR-Cas and indicators of horizontal gene transfer, and found that pathogens with a CRISPR-Cas system were less likely to carry antibiotic resistance genes than those lacking this defence system. Analysis of the mobile genetic elements targeted by CRISPR-Cas supports a model where this host defence system blocks important vectors of antibiotic resistance. These results suggest a potential “immunocompromised” state for multidrug-resistant strains that may be exploited in tailored interventions that rely on mobile genetic elements, such as phage or phagemids, to treat infections caused by bacterial pathogens.

scholarly journals Cargo Genes of Tn 7 -Like Transposons Comprise an Enormous Diversity of Defense Systems, Mobile Genetic Elements, and Antibiotic Resistance Genes

mBio ◽  
2021 ◽  
Author(s):  
Sean Benler ◽  
Guilhem Faure ◽  
Han Altae-Tran ◽  
Sergey Shmakov ◽  
Feng Zheng ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Defense Systems

Transposons are major vehicles of horizontal gene transfer that, in addition to genes directly involved in transposition, carry cargo genes. However, characterization of these genes is hampered by the difficulty of identification of transposon boundaries.

scholarly journals A mobile genetic element increases bacterial host fitness by manipulating development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Joshua M Jones ◽  
Ilana Grinberg ◽  
Avigdor Eldar ◽  
Alan D Grossman
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Mobile Genetic Elements ◽  
Selective Advantage ◽  
Host Cells ◽  
Bacterial Host ◽  
Host Fitness ◽  
Genetic Elements ◽  
Necessary And Sufficient ◽  
Integrative And Conjugative Element

Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.

scholarly journals Disentangling the effects of selection and loss bias on gene dynamics

2017 ◽  
Author(s):  
Jaime Iranzo ◽  
José A. Cuesta ◽  
Susanna Manrubia ◽  
Mikhail I. Katsnelson ◽  
Eugene V. Koonin
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Genome Size ◽  
Mobile Genetic Elements ◽  
Loss Ratio ◽  
Effective Population ◽  
Strong Selection ◽  
Genetic Elements ◽  
Defense Systems ◽  
Parasite Defense

ABSTRACTWe combine mathematical modelling of genome evolution with comparative analysis of prokaryotic genomes to estimate the relative contributions of selection and intrinsic loss bias to the evolution of different functional classes of genes and mobile genetic elements (MGE). An exact solution for the dynamics of gene family size was obtained under a linear duplication-transfer-loss model with selection. With the exception of genes involved in information processing, particularly translation, which are maintained by strong selection, the average selection coefficient for most non-parasitic genes is low albeit positive, compatible with the observed positive correlation between genome size and effective population size. Free-living microbes evolve under stronger selection for gene retention than parasites. Different classes of MGE show a broad range of fitness effects, from the nearly neutral transposons to prophages, which are actively eliminated by selection. Genes involved in anti-parasite defense, on average, incur a fitness cost to the host that is at least as high as the cost of plasmids. This cost is probably due to the adverse effects of autoimmunity and curtailment of horizontal gene transfer caused by the defense systems and selfish behavior of some of these systems, such as toxin-antitoxin and restriction-modification modules. Transposons follow a biphasic dynamics, with bursts of gene proliferation followed by decay in the copy number that is quantitatively captured by the model. The horizontal gene transfer to loss ratio, but not the duplication to loss ratio, correlates with genome size, potentially explaining the increased abundance of neutral and costly elements in larger genomes.SIGNIFICANCEEvolution of microbes is dominated by horizontal gene transfer and the incessant host-parasite arms race that promotes the evolution of diverse anti-parasite defense systems. The evolutionary factors governing these processes are complex and difficult to disentangle but the rapidly growing genome databases provide ample material for testing evolutionary models. Rigorous mathematical modeling of evolutionary processes, combined with computer simulation and comparative genomics, allowed us to elucidate the evolutionary regimes of different classes of microbial genes. Only genes involved in key informational and metabolic pathways are subject to strong selection whereas most of the others are effectively neutral or even burdensome. Mobile genetic elements and defense systems are costly, supporting the understanding that their evolution is governed by the same factors.

scholarly journals Horizontal Gene Transfer of Antibiotic Resistance from Acinetobacter baylyi to Escherichia coli on Lettuce and Subsequent Antibiotic Resistance Transmission to the Gut Microbiome

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Marlène Maeusli ◽  
Bosul Lee ◽  
Sarah Miller ◽  
Zeferino Reyna ◽  
Peggy Lu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Acinetobacter Baylyi ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Plant Foods ◽  
Link Type

ABSTRACT Agricultural use of antibiotics is recognized by the U.S. Centers for Disease Control and Prevention as a major contributor to antibiotic-resistant infections. While most One Health attention has been on the potential for antibiotic resistance transmission from livestock and contaminated meat products to people, plant foods are fundamental to the food chain for meat eaters and vegetarians alike. We hypothesized that environmental bacteria that colonize plant foods may serve as platforms for the persistence of antibiotic-resistant bacteria and for horizontal gene transfer of antibiotic-resistant genes. Donor Acinetobacter baylyi and recipient Escherichia coli were cocultured in vitro, in planta on lettuce, and in vivo in BALB/c mice. We showed that nonpathogenic, environmental A. baylyi is capable of transferring plasmids conferring antibiotic resistance to E. coli clinical isolates on lettuce leaf discs. Furthermore, transformant E. coli from the in planta assay could then colonize the mouse gut microbiome. The target antibiotic resistance plasmid was identified in mouse feces up to 5 days postinfection. We specifically identified in vivo transfer of the plasmid to resident Klebsiella pneumoniae in the mouse gut. Our findings highlight the potential for environmental bacteria exposed to antibiotics to transmit resistance genes to mammalian pathogens during ingestion of leafy greens. IMPORTANCE Previous efforts have correlated antibiotic-fed livestock and meat products with respective antibiotic resistance genes, but virtually no research has been conducted on the transmission of antibiotic resistance from plant foods to the mammalian gut (C. S. Hölzel, J. L. Tetens, and K. Schwaiger, Pathog Dis 15:671–688, 2018, https://doi.org/10.1089/fpd.2018.2501; C. M. Liu et al., mBio 9:e00470-19, 2018, https://doi.org/10.1128/mBio.00470-18; B. Spellberg et al., NAM Perspectives, 2016, https://doi.org/10.31478/201606d; J. O’Neill, Antimicrobials in agriculture and the environment, 2015; Centers for Disease Control and Prevention, Antibiotic resistance threats in the United States, 2019). Here, we sought to determine if horizontal transmission of antibiotic resistance genes can occur between lettuce and the mammalian gut microbiome, using a mouse model. Furthermore, we have created a new model to study horizontal gene transfer on lettuce leaves using an antibiotic-resistant transformant of A. baylyi (AbzeoR).

scholarly journals Staphylococcus edaphicus sp. nov., Isolated in Antarctica, Harbors the mecC Gene and Genomic Islands with a Suspected Role in Adaptation to Extreme Environments

2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Roman Pantůček ◽  
Ivo Sedláček ◽  
Adéla Indráková ◽  
Veronika Vrbovská ◽  
Ivana Mašlaňová ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
New Species ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Novel Species ◽  
Extreme Environments ◽  
Mobile Genetic Elements ◽  
Whole Genome ◽  
Content Type ◽  
Genetic Elements

ABSTRACT Two Gram-stain-positive, coagulase-negative staphylococcal strains were isolated from abiotic sources comprising stone fragments and sandy soil in James Ross Island, Antarctica. Here, we describe properties of a novel species of the genus Staphylococcus that has a 16S rRNA gene sequence nearly identical to that of Staphylococcus saprophyticus. However, compared to S. saprophyticus and the next closest relatives, the new species demonstrates considerable phylogenetic distance at the whole-genome level, with an average nucleotide identity of <85% and inferred DNA-DNA hybridization of <30%. It forms a separate branch in the S. saprophyticus phylogenetic clade as confirmed by multilocus sequence analysis of six housekeeping genes, rpoB, hsp60, tuf, dnaJ, gap, and sod. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and key biochemical characteristics allowed these bacteria to be distinguished from their nearest phylogenetic neighbors. In contrast to S. saprophyticus subsp. saprophyticus, the novel strains are pyrrolidonyl arylamidase and β-glucuronidase positive and β-galactosidase negative, nitrate is reduced, and acid produced aerobically from d-mannose. Whole-genome sequencing of the 2.69-Mb large chromosome revealed the presence of a number of mobile genetic elements, including the 27-kb pseudo-staphylococcus cassette chromosome mec of strain P5085T (ψSCCmec P5085), harboring the mecC gene, two composite phage-inducible chromosomal islands probably essential to adaptation to extreme environments, and one complete and one defective prophage. Both strains are resistant to penicillin G, ampicillin, ceftazidime, methicillin, cefoxitin, and fosfomycin. We hypothesize that antibiotic resistance might represent an evolutionary advantage against beta-lactam producers, which are common in a polar environment. Based on these results, a novel species of the genus Staphylococcus is described and named Staphylococcus edaphicus sp. nov. The type strain is P5085T (= CCM 8730T = DSM 104441T). IMPORTANCE The description of Staphylococcus edaphicus sp. nov. enables the comparison of multidrug-resistant staphylococci from human and veterinary sources evolved in the globalized world to their geographically distant relative from the extreme Antarctic environment. Although this new species was not exposed to the pressure of antibiotic treatment in human or veterinary practice, mobile genetic elements carrying antimicrobial resistance genes were found in the genome. The genomic characteristics presented here elucidate the evolutionary relationships in the Staphylococcus genus with a special focus on antimicrobial resistance, pathogenicity, and survival traits. Genes encoded on mobile genetic elements were arranged in unique combinations but retained conserved locations for the integration of mobile genetic elements. These findings point to enormous plasticity of the staphylococcal pangenome, shaped by horizontal gene transfer. Thus, S. edaphicus can act not only as a reservoir of antibiotic resistance in a natural environment but also as a mediator for the spread and evolution of resistance genes.

scholarly journals Prediction of prophages and their host ranges in pathogenic and commensal Neisseria species

2021 ◽  
Author(s):  
Giulia Orazi ◽  
Alan J Collins ◽  
Rachel J Whitaker
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Bacterial Genome ◽  
Mobile Genetic Elements ◽  
Pathogenic Species ◽  
Chromosomal Dna ◽  
Bacterial Physiology ◽  
Neisseria Species ◽  
Genetic Elements ◽  
Commensal Neisseria

The genus Neisseria includes two pathogenic species, N. gonorrhoeae and N. meningitidis, and numerous commensal species. Neisseria species frequently exchange DNA with one other, primarily via transformation and homologous recombination, and via multiple types of mobile genetic elements (MGEs). Few Neisseria bacteriophages (phages) have been identified and their impact on bacterial physiology is poorly understood. Furthermore, little is known about the range of species that Neisseria phages can infect. In this study, we used three virus prediction tools to scan 248 genomes of 21 different Neisseria species and identified 1302 unique predicted prophages. Using comparative genomics, we found that many predictions are dissimilar from other prophages and MGEs previously described to infect Neisseria species. We also identified similar predicted prophages in genomes of different Neisseria species. Additionally, we examined CRISPR-Cas targeting of each Neisseria genome and predicted prophage. While CRISPR targeting of chromosomal DNA appears to be common among several Neisseria species, we found that 20% of the prophages we predicted are targeted significantly more than the rest of the bacterial genome in which they were identified (i.e., backbone). Furthermore, many predicted prophages are targeted by CRISPR spacers encoded by other species. We then used these results to infer additional host species of known Neisseria prophages and predictions that are highly targeted relative to the backbone. Together, our results suggest that we have identified novel Neisseria prophages, several of which may infect multiple Neisseria species. These findings have important implications for understanding horizontal gene transfer between members of this genus. IMPORTANCE: Drug-resistant N. gonorrhoeae is a major threat to human health. Commensal Neisseria species are thought to serve as reservoirs of antibiotic resistance and virulence genes for the pathogenic species N. gonorrhoeae and N. meningitidis. Therefore, it is important to understand both the diversity of mobile genetic elements (MGEs) that can mediate horizontal gene transfer within this genus, and the breadth of species these MGEs can infect. In particular, few bacteriophages (phages) have been identified and characterized in Neisseria species. In this study, we identified a large number of candidate phages integrated within the genomes of commensal and pathogenic Neisseria species, many of which appear to be novel phages. Importantly, we discovered extensive interspecies targeting of predicted phages by Neisseria CRISPR-Cas systems, which may reflect their movement between different species. Uncovering the diversity and host range of phages is essential for understanding how they influence the evolution of their microbial hosts.

scholarly journals Versatile Cas9-Driven Subpopulation Selection Toolbox forLactococcus lactis

2018 ◽  
Vol 84 (8) ◽  
Author(s):  
Simon van der Els ◽  
Jennelle K. James ◽  
Michiel Kleerebezem ◽  
Peter A. Bron
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Lactococcus Lactis ◽  
Mobile Genetic Elements ◽  
Broad Host Range ◽  
Content Type ◽  
Genetic Elements ◽  
Wide Range ◽  
Dairy Fermentation ◽  
Selection Of

ABSTRACTCRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy speciesLactococcus lactis. The Cas9 expression vector pLABTarget, encoding theStreptocccus pyogenesCas9 under the control of a constitutive promoter, was constructed, allowing plug and play introduction of short guide RNA (sgRNA) sequences to target specific genetic loci. Introduction of apepN-targeting derivative of pLABTarget intoL. lactisstrain MG1363 led to a strong reduction in the number of transformants obtained, which did not occur in apepNdeletion derivative of the same strain, demonstrating the specificity and lethality of the Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the same pLABTarget derivative allowed the selection of apepNdeletion subpopulation from its corresponding single-crossover plasmid integrant precursor, accelerating the construction and selection of gene-specific deletion derivatives inL. lactis. Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic elements, allowed the effective curing of plasmids, prophages, and integrative conjugative elements (ICEs). These results establish that pLABTarget enables the effective exploitation of Cas9 targeting inL. lactis, while the broad-host-range vector used suggests that this toolbox could readily be expanded to other Gram-positive bacteria.IMPORTANCEMobile genetic elements inLactococcus lactisand other lactic acid bacteria (LAB) play an important role in dairy fermentation, having both positive and detrimental effects during the production of fermented dairy products. The pLABTarget vector offers an efficient cloning platform for Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic elements enabled their effective curing, which is of particular interest in the context of potentially problematic prophages present in a strain. Moreover, Cas9 targeting of other mobile genetic elements enables the deciphering of their contribution to dairy fermentation processes and further establishment of their importance for product characteristics.

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