Browse
Submit Data
Databases
API
Help

Dataset Information

33 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evolution of Bacterial Cross-Resistance to Lytic Phages and Albicidin Antibiotic.

ABSTRACT: Due to concerns over the global increase of antibiotic-resistant bacteria, alternative antibacterial strategies, such as phage therapy, are increasingly being considered. However, evolution of bacterial resistance to new therapeutics is almost a certainty; indeed, it is possible that resistance to alternative treatments might result in an evolved trade-up such as enhanced antibiotic resistance. Here, we hypothesize that selection for Escherichia coli bacteria to resist phage T6, phage U115, or albicidin, a DNA gyrase inhibitor, should often result in a pleiotropic trade-up in the form of cross-resistance, because all three antibacterial agents interact with the Tsx porin. Selection imposed by any one of the antibacterials resulted in cross-resistance to all three of them, in each of the 29 spontaneous bacterial mutants examined in this study. Furthermore, cross-resistance did not cause measurable fitness (growth) deficiencies for any of the bacterial mutants, when competed against wild-type E. coli in both low-resource and high-resource environments. A combination of whole-genome and targeted sequencing confirmed that mutants differed from wild-type E. coli via change(s) in the tsx gene. Our results indicate that evolution of cross-resistance occurs frequently in E. coli subjected to independent selection by phage T6, phage U115 or albicidin. This study cautions that deployment of new antibacterial therapies such as phage therapy, should be preceded by a thorough investigation of evolutionary consequences of the treatment, to avoid the potential for evolved trade-ups.

SUBMITTER: Kortright KE

PROVIDER: S-EPMC8245764 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Phages limit the evolution of bacterial antibiotic resistance in experimental microcosms.

Project description:The evolution of multi-antibiotic resistance in bacterial pathogens, often resulting from de novo mutations, is creating a public health crisis. Phages show promise for combating antibiotic-resistant bacteria, the efficacy of which, however, may also be limited by resistance evolution. Here, we suggest that phages may be used as supplements to antibiotics in treating initially sensitive bacteria to prevent resistance evolution, as phages are unaffected by most antibiotics and there should be little cross-resistance to antibiotics and phages. In vitro experiments using the bacterium Pseudomonas fluorescens, a lytic phage, and the antibiotic kanamycin supported this prediction: an antibiotic-phage combination dramatically decreased the chance of bacterial population survival that indicates resistance evolution, compared with antibiotic treatment alone, whereas the phage alone did not affect bacterial survival. This effect of the combined treatment in preventing resistance evolution was robust to immigration of bacteria from an untreated environment, but not to immigration from environment where the bacteria had coevolved with the phage. By contrast, an isogenic hypermutable strain constructed from the wild-type P. fluorescens evolved resistance to all treatments regardless of immigration, but typically suffered very large fitness costs. These results suggest that an antibiotic-phage combination may show promise as an antimicrobial strategy.

| S-EPMC3461140 | biostudies-literature

Lytic phages obscure the cost of antibiotic resistance in Escherichia coli.

Project description:The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods.

| S-EPMC4817697 | biostudies-literature

Exposure to phages has little impact on the evolution of bacterial antibiotic resistance on drug concentration gradients.

Project description:The use of phages for treating bacterial pathogens has recently been advocated as an alternative to antibiotic therapy. Here, we test a hypothesis that bacteria treated with phages may show more limited evolution of antibiotic resistance as the fitness costs of resistance to phages may add to those of antibiotic resistance, further reducing the growth performance of antibiotic-resistant bacteria. We did this by studying the evolution of phage-exposed and phage-free Pseudomonas fluorescens cultures on concentration gradients of single drugs, including cefotaxime, chloramphenicol, and kanamycin. During drug treatment, the level of bacterial antibiotic resistance increased through time and was not affected by the phage treatment. Exposure to phages did not cause slower growth in antibiotic-resistant bacteria, although it did so in antibiotic-susceptible bacteria. We observed significant reversion of antibiotic resistance after drug use being terminated, and the rate of reversion was not affected by the phage treatment. The results suggest that the fitness costs caused by resistance to phages are unlikely to be an important constraint on the evolution of bacterial antibiotic resistance in heterogeneous drug environments. Further studies are needed for the interaction of fitness costs of antibiotic resistance with other factors.

| S-EPMC3962299 | biostudies-literature

Molecular insights into antibiotic resistance - how a binding protein traps albicidin.

Project description:The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs.

| S-EPMC6078987 | biostudies-literature

Fight evolution with evolution: plasmid-dependent phages with a wide host range prevent the spread of antibiotic resistance.

Project description:The emergence of pathogenic bacteria resistant to multiple antibiotics is a serious worldwide public health concern. Whenever antibiotics are applied, the genes encoding for antibiotic resistance are selected for within bacterial populations. This has led to the prevalence of conjugative plasmids that carry resistance genes and can transfer themselves between diverse bacterial groups. In this study, we investigated whether it is feasible to attempt to prevent the spread of antibiotic resistances with a lytic bacteriophage, which can replicate in a wide range of gram-negative bacteria harbouring conjugative drug resistance-conferring plasmids. The counter-selection against the plasmid was shown to be effective, reducing the frequency of multidrug-resistant bacteria that formed via horizontal transfer by several orders of magnitude. This was true also in the presence of an antibiotic against which the plasmid provided resistance. Majority of the multiresistant bacteria subjected to phage selection also lost their conjugation capability. Overall this study suggests that, while we are obligated to maintain the selection for the spread of the drug resistances, the 'fight evolution with evolution' approach could help us even out the outcome to our favour.

| S-EPMC3779093 | biostudies-literature

Plasticity and stereotypic rewiring of the transcriptome upon bacterial evolution of antibiotic resistance

Project description:Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.

2023-01-26 | GSE223493 | GEO

Bacterial motility can govern the dynamics of antibiotic resistance evolution.

Project description:Spatial heterogeneity in antibiotic concentrations is thought to accelerate the evolution of antibiotic resistance, but current theory and experiments have overlooked the effect of cell motility on bacterial adaptation. Here, we study bacterial evolution in antibiotic landscapes with a quantitative model where bacteria evolve under the stochastic processes of proliferation, death, mutation and migration. Numerical and analytical results show that cell motility can both accelerate and decelerate bacterial adaptation by affecting the degree of genotypic mixing and ecological competition. Moreover, we find that for sufficiently high rates, cell motility can limit bacterial survival, and we derive conditions for all these regimes. Similar patterns are observed in more complex scenarios, namely where bacteria can bias their motion in chemical gradients (chemotaxis) or switch between motility phenotypes either stochastically or in a density-dependent manner. Overall, our work reveals limits to bacterial adaptation in antibiotic landscapes that are set by cell motility.

| S-EPMC10495427 | biostudies-literature

DNA gyrase from the albicidin producer Xanthomonas albilineans has multiple-antibiotic-resistance and unusual enzymatic properties.

Project description:The sugarcane pathogen Xanthomonas albilineans produces a family of antibiotics and phytotoxins termed albicidins, which inhibit plant and bacterial DNA gyrase supercoiling activity, with a 50% inhibitory concentration (50 nM) comparable to those of coumarins and quinolones. Here we show that X. albilineans has an unusual, antibiotic-resistant DNA gyrase. The X. albilineans gyrA and gyrB genes are not clustered with previously described albicidin biosynthesis and self-protection genes. The GyrA and GyrB products differ from Escherichia coli homologues through several insertions and through changes in several amino acid residues implicated in quinolone and coumarin resistance. Reconstituted X. albilineans DNA gyrase showed 20- to 25-fold-higher resistance than E. coli DNA gyrase to albicidin and ciprofloxacin and 8-fold-higher resistance to novobiocin in the supercoiling assay. The X. albilineans DNA gyrase is unusual in showing a high degree of distributive supercoiling and little DNA relaxation activity. X. albilineans GyrA (XaA) forms a functional gyrase heterotetramer with E. coli GyrB (EcB) and can account for albicidin and quinolone resistance and low levels of relaxation activity. XaB probably contributes to both coumarin resistance and the distributive supercoiling pattern. Although XaB shows fewer apparent changes relative to EcB, the EcA.XaB hybrid relaxed DNA in the presence or absence of ATP and was unable to supercoil. A fuller understanding of structural differences between albicidin-sensitive and -resistant gyrases may provide new clues into features of the enzyme amenable to interference by novel antibiotics.

| S-EPMC2292561 | biostudies-literature

Intermittent antibiotic treatment of bacterial biofilms favors the rapid evolution of resistance.

Project description:Bacterial antibiotic resistance is a global health concern of increasing importance and intensive study. Although biofilms are a common source of infections in clinical settings, little is known about the development of antibiotic resistance within biofilms. Here, we use experimental evolution to compare selection of resistance mutations in planktonic and biofilm Escherichia coli populations exposed to clinically relevant cycles of lethal treatment with the aminoglycoside amikacin. Consistently, mutations in sbmA, encoding an inner membrane peptide transporter, and fusA, encoding the essential elongation factor G, are rapidly selected in biofilms, but not in planktonic cells. This is due to a combination of enhanced mutation rate, increased adhesion capacity and protective biofilm-associated tolerance. These results show that the biofilm environment favors rapid evolution of resistance and provide new insights into the dynamic evolution of antibiotic resistance in biofilms.

| S-EPMC10020551 | biostudies-literature

Bacterial evolution of antibiotic hypersensitivity.

Project description:The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection.

| S-EPMC3817406 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data