The Effect of Horizontal Gene Transfer on the Dynamics of Antibiotic Drug Resistance in a Unicellular Population with a Dynamic Fitness Landscape, Repression and De-repression

Antibiotic drug resistance spreads through horizontal gene transfer (HGT) via bacterial conjugation in unicellular populations of bacteria. Consequently, the efficiency of antibiotics is limited and the expected “grace period” of novel antibiotics is typically quite short. One of the mechanisms that allow the accelerated adaptation of bacteria to antibiotics is bacterial conjugation. However, bacterial conjugation is regulated by several biological factors, with one of the most important ones being repression and de-repression. In recent work, we have studied the effects that repression and de-repression on the mutation-selection balance of an HGT-enabled bacterial population in a static environment. Two of our main findings were that conjugation has a deleterious effect on the mean fitness of the population and that repression is expected to allow a restoration of the fitness cost due to plasmid hosting. Here, we consider the effect that conjugation-mediated HGT has on the speed of adaptation in a dynamic environment and the effect that repression will have on the dynamics of antibiotic drug resistance. We find that, the effect of repression is dynamic in its possible outcome, that a conjugators to non-conjugators phase transition exists in a dynamic landscape as we have previously found for a static landscape and we quantify the time required for a unicellular population to adapt to a new antibiotic in a periodically changing fitness landscape. Our results also confirmed that HGT accelerates adaptation for a population of prokaryotes which agrees with current knowledge, that HGT rates increase when a population is put under stress.

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Horizontal gene transfer of a unique nif island drives convergent evolution of free-living N2-fixing Bradyrhizobium

10.1101/2021.02.03.429501 ◽

2021 ◽

Author(s):

Jinjin Tao ◽

Sishuo Wang ◽

Tianhua Liao ◽

Haiwei Luo

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Agricultural Research ◽

Current Knowledge ◽

Gene Clusters ◽

Soil Samples ◽

Genomic Context ◽

Free Living ◽

Phylogenomic Analyses ◽

Conserved Gene

SummaryThe alphaproteobacterial genus Bradyrhizobium has been best known as N2-fixing members that nodulate legumes, supported by the nif and nod gene clusters. Recent environmental surveys show that Bradyrhizobium represents one of the most abundant free-living bacterial lineages in the world’s soils. However, our understanding of Bradyrhizobium comes largely from symbiotic members, biasing the current knowledge of their ecology and evolution. Here, we report the genomes of 88 Bradyrhizobium strains derived from diverse soil samples, including both nif-carrying and non-nif-carrying free-living (nod free) members. Phylogenomic analyses of these and 252 publicly available Bradyrhizobium genomes indicate that nif-carrying free-living members independently evolved from symbiotic ancestors (carrying both nif and nod) multiple times. Intriguingly, the nif phylogeny shows that all nif-carrying free-living members comprise a cluster which branches off earlier than most symbiotic lineages. These results indicate that horizontal gene transfer (HGT) promotes nif expansion among the free-living Bradyrhizobium and that the free-living nif cluster represents a more ancestral version compared to that in symbiotic lineages. Further evidence for this rampant HGT is that the nif in free-living members consistently co-locate with several important genes involved in coping with oxygen tension which are missing from symbiotic members, and that while in free-living Bradyrhizobium nif and the co-locating genes show a highly conserved gene order, they each have distinct genomic context. Given the dominance of Bradyrhizobium in world’s soils, our findings have implications for global nitrogen cycles and agricultural research.

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Horizontal gene transfer among microorganisms in food: Current knowledge and future perspectives

Food Microbiology ◽

10.1016/j.fm.2014.04.004 ◽

2014 ◽

Vol 42 ◽

pp. 232-243 ◽

Cited By ~ 58

Author(s):

Franca Rossi ◽

Lucia Rizzotti ◽

Giovanna E. Felis ◽

Sandra Torriani

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Current Knowledge ◽

Future Perspectives

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Dissemination of the blaNDM-5 Gene via IncX3-Type Plasmid among Enterobacteriaceae in Children

mSphere ◽

10.1128/msphere.00699-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 2

Author(s):

Dongxing Tian ◽

Bingjie Wang ◽

Hong Zhang ◽

Fen Pan ◽

Chun Wang ◽

...

Keyword(s):

Escherichia Coli ◽

Drug Resistance ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Klebsiella Pneumoniae ◽

Pediatric Patients ◽

Transmission Mechanism ◽

Klebsiella Aerogenes ◽

Content Type ◽

E Coli

ABSTRACT The continuous emergence of novel New Delhi metallo-β-lactamase-5 (NDM-5)-producing Enterobacteriaceae isolates is receiving more and more public attention. Twenty-two NDM-5-producing strains were identified from 146 carbapenemase-producing Enterobacteriaceae (CRE) strains isolated from pediatric patients between January and March 2017, indicating that the blaNDM-5 gene has spread to children. All 22 isolates, including 16 Klebsiella pneumoniae strains, four Klebsiella aerogenes strains, and two Escherichia coli strains, showed significantly high resistance to β-lactam antibiotics (except aztreonam) but remained susceptible to tigecycline and colistin. K. pneumoniae and K. aerogenes strains were respectively defined as homologous clonal isolates by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) results confirmed the genetic relatedness with all K. pneumoniae strains belonging to sequence type (ST) 48. Two E. coli isolates (ST617 and ST1236) were considered genetically unrelated. Twenty-two blaNDM-5 plasmids were positive for the IncX3 amplicon and showed almost identical profiles after digestion with HindIII and EcoRI. Four representative strains (K. pneumoniae K725, K. aerogenes CR33, E. coli Z214, and E. coli Z244) were selected for further study. Plasmids harboring blaNDM-5 showed strong stability in both clinical isolates and transconjugants, without apparent plasmid loss after 100 serial generations. S1-PFGE followed by Southern blot analysis demonstrated that the blaNDM-5 gene was located on an ∼46-kb plasmid. Plasmid sequences of pNDM-K725, pNDM-CR33, and pNDM-Z214 were almost identical but were slightly different from that of pNDM-Z244. Compared with pNDM-Z244, ΔISAba125 and partial copies of IS3000 were missing. The genetic backgrounds of the blaNDM-5 gene in four strains were slightly different from that of the typical pNDM_MGR194. This study comprehensively characterized the horizontal gene transfer of the blaNDM-5 gene among different Enterobacteriaceae isolates in pediatric patients, and the IncX3-type plasmid was responsible for the spread. IMPORTANCE The emergence of CRE strains resistant to multiple antibiotics is considered a substantial threat to human health. Therefore, all the efforts to provide a detailed molecular transmission mechanism of specific drug resistance can contribute positively to prevent the further spread of multidrug-resistant bacteria. Although the new superbug harboring blaNDM-5 has been reported in many countries, it was mostly identified among E. coli strains, and the gene transfer mechanism has not been fully recognized and studied. In this work, we identified 22 blaNDM-5-positive strains in different species of Enterobacteriaceae, including 16 Klebsiella pneumoniae strains, four Klebsiella aerogenes strains, and two Escherichia coli strains, which indicated the horizontal gene transfer of blaNDM-5 among Enterobacteriaceae strains in pediatric patients. Moreover, blaNDM-5 was located on a 46-kb IncX3 plasmid, which is possibly responsible for this widespread horizontal gene transfer. The different genetic contexts of the blaNDM-5 gene indicated some minor evolutions of the plasmid, based on the complete sequences of the blaNDM-5 plasmids. These findings are of great significance to understand the transmission mechanism of drug resistance genes, develop anti-infection treatment, and take effective infection control measures.

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Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

mBio ◽

10.1128/mbio.01032-15 ◽

2015 ◽

Vol 6 (5) ◽

Cited By ~ 35

Author(s):

María Getino ◽

David J. Sanabria-Ríos ◽

Raúl Fernández-López ◽

Javier Campos-Gómez ◽

José M. Sánchez-López ◽

...

Keyword(s):

Fatty Acids ◽

Antibiotic Resistance ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Resistant Bacteria ◽

Aliphatic Chain ◽

Bacterial Conjugation ◽

Human Pathogens

ABSTRACT Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.

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Gene exchange networks define species-like units in marine prokaryotes

10.1101/2020.09.10.291518 ◽

2020 ◽

Author(s):

R. Stepanauskas ◽

J.M. Brown ◽

U. Mai ◽

O. Bezuidt ◽

M. Pachiadaki ◽

...

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Dynamic Environment ◽

Evolutionary Process ◽

Gene Exchange ◽

Marine Microorganisms ◽

Nucleotide Difference ◽

Tropical Ocean ◽

Exchange Networks ◽

Taxonomic Marker

SUMMARYAlthough horizontal gene transfer is recognized as a major evolutionary process in Bacteria and Archaea, its general patterns remain elusive, due to difficulties tracking genes at relevant resolution and scale within complex microbiomes. To circumvent these challenges, we analyzed a randomized sample of >12,000 genomes of individual cells of Bacteria and Archaea in the tropical and subtropical ocean - a well-mixed, global environment. We found that marine microorganisms form gene exchange networks (GENs) within which transfers of both flexible and core genes are frequent, including the rRNA operon that is commonly used as a conservative taxonomic marker. The data revealed efficient gene exchange among genomes with <28% nucleotide difference, indicating that GENs are much broader lineages than the nominal microbial species, which are currently delineated at 4-6% nucleotide difference. The 42 largest GENs accounted for 90% of cells in the tropical ocean microbiome. Frequent gene exchange within GENs helps explain how marine microorganisms maintain millions of rare genes and adapt to a dynamic environment despite extreme genome streamlining of their individual cells. Our study suggests that sharing of pangenomes through horizontal gene transfer is a defining feature of fundamental evolutionary units in marine planktonic microorganisms and, potentially, other microbiomes.

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Horizontal gene transfer contributes to virulence and antibiotic resistance of Vibrio harveyi 345 based on complete genome sequence analysis

10.21203/rs.2.13151/v3 ◽

2019 ◽

Author(s):

Yiqin Deng ◽

Haidong Xu ◽

Youlu Su ◽

Songlin Liu ◽

Liwen Xu ◽

...

Keyword(s):

Climate Change ◽

Drug Resistance ◽

Antibiotic Resistance ◽

Gene Transfer ◽

Antimicrobial Resistance ◽

Horizontal Gene Transfer ◽

Genome Sequence ◽

Resistance Genes ◽

Complete Genome ◽

Vibrio Harveyi

Abstract Background Horizontal gene transfer (HGT), which is affected by environmental pollution and climate change, promotes genetic communication, changing bacterial pathogenicity and drug resistance. However, few studies have been conducted on the effect of HGT on the high pathogenicity and drug resistance of the opportunistic pathogen Vibrio harveyi .Results V. harveyi 345 that was multidrug resistant and infected Epinephelus oanceolutus was isolated from a diseased organism in Shenzhen, Southern China, an important and contaminated aquaculture area. Analysis of the entire genome sequence predicted 5,678 genes including 487 virulence genes contributing to bacterial pathogenesis and 25 antibiotic-resistance genes (ARGs) contributing to antimicrobial resistance. Five ARGs ( tetm , tetb , qnrs , dfra17 , and sul2 ) and one virulence gene (CU052_28670) on the pAQU-type plasmid p345-185, provided direct evidence for HGT. Comparative genome analysis of 31 V. harveyi strains indicated that 217 genes and 7 gene families, including a class C beta-lactamase gene, a virulence-associated protein D gene, and an OmpA family protein gene were specific to strain V. harveyi 345. These genes could contribute to HGT or be horizontally transferred from other bacteria to enhance the virulence or antibiotic resistance of 345. Mobile genetic elements in 71 genomic islands encoding virulence factors for three type III secretion proteins and 13 type VI secretion system proteins, and two incomplete prophage sequences were detected that could be HGT transfer tools. Evaluation of the complete genome of V. harveyi 345 and comparative genomics indicated genomic exchange, especially exchange of pathogenic genes and drug-resistance genes by HGT contributing to pathogenicity and drug resistance. Climate change and continued environmental deterioration are expected to accelerate the HGT of V. harveyi , increasing its pathogenicity and drug resistance.Conclusion This study provides timely information for further analysis of V. harveyi pathogenesis and antimicrobial resistance and developing pollution control measurements for coastal areas.

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Environment-dependent fitness gains can be driven by horizontal gene transfer of transporter-encoding genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1815994116 ◽

2019 ◽

Vol 116 (12) ◽

pp. 5613-5622 ◽

Cited By ~ 15

Author(s):

David S. Milner ◽

Victoria Attah ◽

Emily Cook ◽

Finlay Maguire ◽

Fiona R. Savory ◽

...

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Fitness Landscape ◽

Single Gene ◽

Transporter Gene ◽

Metabolic Potential ◽

Gene Acquisition ◽

A Genome ◽

Complex Polymers ◽

Encoding Genes

Many microbes acquire metabolites in a “feeding” process where complex polymers are broken down in the environment to their subunits. The subsequent uptake of soluble metabolites by a cell, sometimes called osmotrophy, is facilitated by transporter proteins. As such, the diversification of osmotrophic microorganisms is closely tied to the diversification of transporter functions. Horizontal gene transfer (HGT) has been suggested to produce genetic variation that can lead to adaptation, allowing lineages to acquire traits and expand niche ranges. Transporter genes often encode single-gene phenotypes and tend to have low protein–protein interaction complexity and, as such, are potential candidates for HGT. Here we test the idea that HGT has underpinned the expansion of metabolic potential and substrate utilization via transfer of transporter-encoding genes. Using phylogenomics, we identify seven cases of transporter-gene HGT between fungal phyla, and investigate compatibility, localization, function, and fitness consequences when these genes are expressed inSaccharomyces cerevisiae. Using this approach, we demonstrate that the transporters identified can alter how fungi utilize a range of metabolites, including peptides, polyols, and sugars. We then show, for one model gene, that transporter gene acquisition by HGT can significantly alter the fitness landscape ofS. cerevisiae. We therefore provide evidence that transporter HGT occurs between fungi, alters how fungi can acquire metabolites, and can drive gain in fitness. We propose a “transporter-gene acquisition ratchet,” where transporter repertoires are continually augmented by duplication, HGT, and differential loss, collectively acting to overwrite, fine-tune, and diversify the complement of transporters present in a genome.

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Modern View on Enterococcus faecalis and Enterococcus faecium Resistance Mechanisms to Antibiotics

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-11-12-38-48 ◽

2021 ◽

Vol 65 (11-12) ◽

pp. 38-48

Author(s):

T. S. Komenkova ◽

E. A. Zaitseva

Keyword(s):

Clinical Practice ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Enterococcus Faecalis ◽

Enterococcus Faecium ◽

Current Knowledge ◽

Common Species ◽

Resistance Mechanisms ◽

Causative Agents ◽

Level Resistance

Enterococci are currently becoming one of the major causative agents of various infectious diseases. Enterococcus faecalis and E.faecium are the most common species causing enterococcal infections. Both species exhibit natural low-level resistance to aminoglycosides, cephalosporins, quinolones, clindamycin, and co-trimoxazole. In addition, the peculiarities of their genome make it easy to acquire resistance to other antibiotics widely used in clinical practice, through mutations or by horizontal gene transfer. The review represents current knowledge about the mechanisms of enterococcal resistance to the most commonly used antibiotics.

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Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits

Virology ◽

10.1016/j.virol.2014.03.023 ◽

2014 ◽

Vol 456-457 ◽

pp. 310-318 ◽

Cited By ~ 3

Author(s):

Sarah Megens ◽

Dolores Vaira ◽

Greet De Baets ◽

Nathalie Dekeersmaeker ◽

Yoeri Schrooten ◽

...

Keyword(s):

Drug Resistance ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Reverse Transcriptase ◽

Human Host ◽

Hiv 1

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Adaptive evolution of hybrid bacteria by horizontal gene transfer

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007873118 ◽

2021 ◽

Vol 118 (10) ◽

pp. e2007873118

Author(s):

Jeffrey J. Power ◽

Fernanda Pinheiro ◽

Simone Pompei ◽

Viera Kovacova ◽

Melih Yüksel ◽

...

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Adaptive Evolution ◽

Gene Networks ◽

Fitness Landscape ◽

Parallel Evolution ◽

Rapid Evolution ◽

Sequence Divergence ◽

Genomic Analysis ◽

Stationary Growth Phase

Horizontal gene transfer (HGT) is an important factor in bacterial evolution that can act across species boundaries. Yet, we know little about rate and genomic targets of cross-lineage gene transfer and about its effects on the recipient organism's physiology and fitness. Here, we address these questions in a parallel evolution experiment with two Bacillus subtilis lineages of 7% sequence divergence. We observe rapid evolution of hybrid organisms: gene transfer swaps ∼12% of the core genome in just 200 generations, and 60% of core genes are replaced in at least one population. By genomics, transcriptomics, fitness assays, and statistical modeling, we show that transfer generates adaptive evolution and functional alterations in hybrids. Specifically, our experiments reveal a strong, repeatable fitness increase of evolved populations in the stationary growth phase. By genomic analysis of the transfer statistics across replicate populations, we infer that selection on HGT has a broad genetic basis: 40% of the observed transfers are adaptive. At the level of functional gene networks, we find signatures of negative, positive, and epistatic selection, consistent with hybrid incompatibilities and adaptive evolution of network functions. Our results suggest that gene transfer navigates a complex cross-lineage fitness landscape, bridging epistatic barriers along multiple high-fitness paths.

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