Dataset Information

Biofilms preserve the transmissibility of a multi-drug resistance plasmid.

ABSTRACT: Self-transmissible multidrug resistance (MDR) plasmids are a major health concern because they can spread antibiotic resistance to pathogens. Even though most pathogens form biofilms, little is known about how MDR plasmids persist and evolve in biofilms. We hypothesize that (i) biofilms act as refugia of MDR plasmids by retaining them in the absence of antibiotics longer than well-mixed planktonic populations and that (ii) the evolutionary trajectories that account for the improvement of plasmid persistence over time differ between biofilms and planktonic populations. In this study, we evolved Acinetobacter baumannii with an MDR plasmid in biofilm and planktonic populations with and without antibiotic selection. In the absence of selection, biofilm populations were better able to maintain the MDR plasmid than planktonic populations. In planktonic populations, plasmid persistence improved rapidly but was accompanied by a loss of genes required for the horizontal transfer of plasmids. In contrast, in biofilms, most plasmids retained their transfer genes, but on average, plasmid, persistence improved less over time. Our results showed that biofilms can act as refugia of MDR plasmids and favor the horizontal mode of plasmid transfer, which has important implications for the spread of MDR.

SUBMITTER: Metzger GA

PROVIDER: S-EPMC9732292 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biofilms preserve the transmissibility of a multi-drug resistance plasmid.

Metzger Genevieve A GA Ridenhour Benjamin J BJ France Michael M Gliniewicz Karol K Millstein Jack J Settles Matthew L ML Forney Larry J LJ Stalder Thibault T Top Eva M EM

NPJ biofilms and microbiomes 20221209 1

Self-transmissible multidrug resistance (MDR) plasmids are a major health concern because they can spread antibiotic resistance to pathogens. Even though most pathogens form biofilms, little is known about how MDR plasmids persist and evolve in biofilms. We hypothesize that (i) biofilms act as refugia of MDR plasmids by retaining them in the absence of antibiotics longer than well-mixed planktonic populations and that (ii) the evolutionary trajectories that account for the improvement of plasmid ...[more]

PMID: 36481746

Similar Datasets

Project description:ObjectivesSurveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs.DesignThis is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients.MethodsThe prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility.ResultsPrevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90?M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads.ConclusionThe significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.

Project description:Antibiotic resistance is a major public health concern due to its association with the loss of efficacy of antimicrobial therapies. Horizontal transfer events may play a significant role in the dissemination of resistant bacterial phenotypes, being mobilizable plasmids a well-known mechanism. In this study, we aimed to gain insights into the genetics underlying the development of antibiotic resistance by Piscirickettsia salmonis isolates, a bacterial fish pathogen and causative agent of salmonid piscirickettsiosis, and the main target of antibiotics used in Chilean salmon farming. We provide experimental evidence that the plasmid p3PS10, which harbors multidrug resistance genes for chloramphenicol (cat2), tetracyclines [tet(31)], aminoglycosides (sat1 and aadA1), and sulfonamides (sul2), is carried by a group of P. salmonis isolates exhibiting a markedly reduced susceptibility to oxytetracycline in vitro (128-256 μg/mL of minimal inhibitory concentration, MIC). Antibiotic susceptibility analysis extended to those antibiotics showed that MIC of chloramphenicol, streptomycin, and sulfamethoxazole/trimethoprim were high, but the MIC of florfenicol remained at the wild-type level. By means of molecular cloning, we demonstrate that those genes encoding putative resistance markers are indeed functional. Interestingly, mating assays clearly show that p3PS10 is able to be transferred into and replicate in different hosts, thereby conferring phenotypes similar to those found in the original host. According to epidemiological data, this strain is distributed across aquaculture settings in southern Chile and is likely to be responsible for oxytetracycline treatment failures. This work demonstrates that P. salmonis is more versatile than it was thought, capable of horizontally transferring DNA, and probably playing a role as a vector of resistance traits among the seawater bacterial population. However, the low transmission frequency of p3PS10 suggests a negligible chance of resistance markers being spread to human pathogens.

Project description:Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections.

Project description:Multidrug-resistant (MDR) hypervirulent Klebsiella pneumoniae (hvKp) sequence type (ST) 23 (MDR-ST23-hvKp) is emerging in China. Despite its increasing importance, this pathogen has not yet been subject to detailed genomic interrogation. We identified 28 ST23 Kp isolated from three hospitals in China. The organisms were subjected to antimicrobial susceptibility testing and whole-genome sequencing (WGS). These novel genomic sequences were analyzed in combination with 218 publicly available genome sequences. We performed molecular serotyping and subtyping, assessed the composition of virulence-associated and antimicrobial resistance (AMR) genes, and determined mobile elements associated with horizontal gene transfer. Two MDR-ST23-hvKp were sequenced by long-read sequencing. The genetic characteristics of MDR and non-MDR isolates were compared. Among the 28 novel ST23 isolates, all were hvKp and 2/28 (7.1%) were MDR-hvKp. From the collection of 246 genomes, KL1 was the predominant serotype (224/246; 91.1%) and the siderophore combination of YbST46-CbST29-AbST1-SmST2 was dominant (101/246; 41.1%); 34/246 (13.8%) organisms belonged to MDR-ST23-hvKp. IncF and IncR plasmid replicons were significantly more prevalent in the MDR group (P < 0.05) than in the non-MDR group. IS26 was commonly involved in AMR acquisition. We observed that the acquisition of AMR genes within the ST23-hvKp was not associated with a loss of virulence genes. A 28-bp fusion site was highly conserved with two copies of the virulence-associated plasmid in ST23-hvKp, and we harbored by some of the IncFII plasmids of MDR-ST23-hvKp. Our data suggest that MDR-ST23-hvKp has undergone multiple independent genetic acquisition and recombination events within different sublineages. Notably, the acquisition of IncFII plasmids and/or IS26 contributed to the horizontal transfer of AMR genes within ST23-hvKp. Genomic surveillance is essential for further tracking of kMDR-ST23-hvKp. IMPORTANCE Hypervirulent Klebsiella pneumoniae (hvKp) has become the dominant pathotype in hospitals recently. The sequence type (ST) 23 hvKp, which are more commonly associated with the community-acquired infections previously, may have the capacity to acquire multidrug-resistant (MDR) phenotypes creating a new "superbug" (MDR-hvKp) in hospital. In the present study, we studied the associations of MDR and hypervirulence among ST23 K. pneumoniae from our strain collection and publicly accessible genome data. By comparative analysis of the carriage of resistance genes, virulence genes plasmid replicon types, and plasmid sequences, we found that IncFII plasmids were significantly more prevalent in MDR isolates and IS26 were commonly involved in resistance gene acquisition. We also discovered new MDR plasmids. These results provided an overview landscape of the genetic elements associated with MDR-ST23-hvKp based on currently accessible genome data and calling for further genomic surveillance and well-designed control studies of MDR-ST23-hvKp.

Dataset Information

Biofilms preserve the transmissibility of a multi-drug resistance plasmid.

Publications

Biofilms preserve the transmissibility of a multi-drug resistance plasmid.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets