Whole-transcriptome analysis after the acquisition of antibiotic resistance of Cronobacter sakazakii: Mechanisms of antibiotic resistance and virulence changes. - Related Documents




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628701.0000Whole-transcriptome analysis after the acquisition of antibiotic resistance of Cronobacter sakazakii: Mechanisms of antibiotic resistance and virulence changes. The emergence of antibiotic-resistant bacteria led to the misuse of antibiotics, resulting in the emergence of more resistant bacteria and continuous improvement in their resistance ability. Cronobacter sakazakii (C. sakazakii) has been considered a pathogen that harms infants. Incidents of C. sakazakii contamination have continued globally, several studies have indicated that C. sakazakii is increasingly resistant to antibiotics. A few studies have explored the mechanism of antibiotic resistance in C. sakazakii, and some have examined the antibiotic resistance and changes in virulence levels. We aimed to investigate the antibiotic resistance mechanism and virulence differences in C. sakazakii. The level of virulence factors of C. sakazakii was modified after induction by antibiotics compared with the antibiotic-sensitive strains, and the XS001-Ofl group had the strongest capacity to produce enterotoxin (85.18 pg/mL) and hemolysin (1.47 ng/mL). The biofilm formation capacity after induction significantly improved. The number of bases and mapped reads in all groups accounted for more than 55 % and 70 %, as detected by transcriptomic analysis. The resistance mechanism of different antibiotics was more common in efflux pumps, cationic antimicrobial peptides, and biofilm formation pathways. The level of antibiotic resistance mainly affected the expression of virulence genes associated with flagella assembly and synthesis.202337981356
628610.9998The mRNA expression of ompF, invA and invE was associated with the ciprofloxacin-resistance in Salmonella. Salmonella developed drug-resistance under durative antibiotic pressures pressure. The widespread prevalence of Salmonella has been associated with not only drug-resistance but also pathogenicity. Outer membrane porin proteins (OMPs) are critical for the drug resistance of bacteria. Virulence genes in Salmonella pathogenicity islands (SPIs) play key roles in the virulence of bacteria. In this study, we analyzed the expression levels of three critical genes in ciprofloxacin-resistant strains and ciprofloxacin-susceptible strains of Salmonella, including outer membrane porin protein F (ompF), virulence genes invA and invE. In the clinical ciprofloxacin-resistant strains of Salmonella, the expression level of ompF was decreased. Meanwhile, the expression levels of invA and invE were decreased except for only one strain, indicating generally decreased virulence. These results were also verified with ciprofloxacin-induced resistant strains. Thus, it was informative for understanding the drug-resistance in Salmonella. Monitoring drug-resistance and virulence relevant genes would be significant in the prevention and control of salmonellosis.202032535789
627920.9997Comparative transcriptomics analyses of the different growth states of multidrug-resistant Acinetobacter baumannii. Multidrug-resistant (MDR) Acinetobacter baumannii is an important bacterial pathogen commonly associated with hospital acquired infections. A. baumannii can remain viable and hence virulent in the environment for a long period of time due primarily to its ability to form biofilms. A total of 459 cases of MDR A. baumannii our hospital collected from March 2014 to March 2015 were examined in this study, and a representative isolate selected for high-throughput mRNA sequencing and comparison of gene expression profiles under the biofilm and exponential growth conditions. Our study found that the same bacteria indeed exhibited differential mRNA expression under different conditions. Compared to the rapidly growing bacteria, biofilm bacteria had 106 genes upregulated and 92 genes downregulated. Bioinformatics analyses suggested that many of these genes are involved in the formation and maintenance of biofilms, whose expression also depends on the environment and specific signaling pathways and transcription factors that are absent in the log phase bacteria. These differentially expressed mRNAs might contribute to A. baumannii's unique pathogenicity and ability to inflict chronic and recurrent infections.201727916419
884230.9997Transcriptomic study of Salmonella enterica subspecies enterica serovar Typhi biofilm. BACKGROUND: Typhoid fever is an acute systemic infection of humans caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). In chronic carriers, the bacteria survive the harsh environment of the gallbladder by producing biofilm. The phenotype of S. Typhi biofilm cells is significantly different from the free-swimming planktonic cells, and studies have shown that they are associated with antibiotic resistance, immune system evasion, and bacterial persistence. However, the mechanism of this transition and the events leading to biofilm formation are unknown. High throughput sequencing was performed to identify the genes involved in biofilm formation and to postulate the mechanism of action. RESULTS: Planktonic S. Typhi cells were cultured using standard nutrient broth whereas biofilm cells were cultured in a stressful environment using high shearing-force and bile to mimic the gallbladder. Sequencing libraries were prepared from S. Typhi planktonic cells and mature biofilm cells using the Illumina HiSeq 2500 platform, and the transcriptome data obtained were processed using Cufflinks bioinformatics suite of programs to investigate differential gene expression between the two phenotypes. A total of 35 up-regulated and 29 down-regulated genes were identified. The identities of the differentially expressed genes were confirmed using NCBI BLAST and their functions were analyzed. The results showed that the genes associated with metabolic processes and biofilm regulations were down-regulated while those associated with the membrane matrix and antibiotic resistance were highly up-regulated. CONCLUSIONS: It is proposed that the biofilm phenotype of S. Typhi allows the bacteria to increase production of the membrane matrix in order to serve as a physical shield and to adhere to surfaces, and enter an energy conservation state in response to the stressful environment. Conversely, the planktonic phenotype allows the bacteria to produce flagella and increase metabolic activity to enable the bacteria to migrate and form new colonies of infection. This data provide a basis for further studies to uncover the mechanism of biofilm formation in S. Typhi and to discover novel genes or pathways associated with the development of the typhoid carrier state.201729089020
897040.9997Transcriptomic Analyses to Unravel Cronobacter sakazakii Resistance Pathways. The proliferation of antibiotic usage has precipitated the emergence of drug-resistant variants of bacteria, thereby augmenting their capacity to withstand pharmaceutical interventions. Among these variants, Cronobacter sakazakii (C. sakazakii), prevalent in powdered infant formula (PIF), poses a grave threat to the well-being of infants. Presently, global contamination by C. sakazakii is being observed. Consequently, research endeavors have been initiated to explore the strain's drug resistance capabilities, alterations in virulence levels, and resistance mechanisms. The primary objective of this study is to investigate the resistance mechanisms and virulence levels of C. sakazakii induced by five distinct antibiotics, while concurrently conducting transcriptomic analyses. Compared to the susceptible strains prior to induction, the drug-resistant strains exhibited differential gene expression, resulting in modifications in the activity of relevant enzymes and biofilm secretion. Transcriptomic studies have shown that the expression of glutathione S-transferase and other genes were significantly upregulated after induction, leading to a notable enhancement in biofilm formation ability, alongside the existence of antibiotic resistance mechanisms associated with efflux pumps, cationic antimicrobial peptides, and biofilm formation pathways. These alterations significantly influence the strain's resistance profile.202439272551
895450.9997Effect of biofilm formation by antimicrobial-resistant gram-negative bacteria in cold storage on survival in dairy processing lines. Antimicrobial-resistant gram-negative bacteria in dairy products can transfer antimicrobial resistance to gut microbiota in humans and can adversely impact the product quality. In this study, we aimed to investigate their distribution in dairy processing lines and evaluate biofilm formation and heat tolerance under dairy processing line-like conditions. Additionally, we compared the relative expression of general and heat stress-related genes as well as spoilage-related gene between biofilm and planktonic cells under consecutive stresses, similar to those in dairy processing lines. Most species of gram-negative bacteria isolated from five different dairy processing plants were resistant to one or more antimicrobials. Biofilm formation by the bacteria at 5 °C increased with the increase in exposure time. Moreover, cells in biofilms remained viable under heat treatment, whereas all planktonic cells of the selected strains died. The expression of heat-shock-related genes significantly increased with heat treatment in the biofilms but mostly decreased in the planktonic cells. Thus, biofilm formation under raw milk storage conditions may improve the tolerance of antimicrobial-resistant gram-negative bacteria to pasteurization, thereby increasing their persistence in dairy processing lines and products. Furthermore, the difference in response to heat stress between biofilm and planktonic cells may be attributed to the differential expression of heat stress-related genes. Therefore, this study contributes to the understanding of how gram-negative bacteria persist under consecutive stresses in dairy processing procedures and the potential mechanism underlying heat tolerance in biofilms.202336436412
457360.9997High pressure processing, acidic and osmotic stress increased resistance to aminoglycosides and tetracyclines and the frequency of gene transfer among strains from commercial starter and protective cultures. This study analyzed the effect of food-related stresses on the expression of antibiotic resistance of starter and protective strains and resistance gene transfer frequency. After exposure to high-pressure processing, acidic and osmotic stress, the expression of genes encoding resistance to aminoglycosides (aac(6')Ie-aph(2″)Ia and aph(3')-IIIa) and/or tetracyclines (tetM) increased. After cold stress, a decrease in the expression level of all tested genes was observed. The results obtained in the gene expression analysis correlated with the results of the phenotype patterns. After acidic and osmotic stresses, a significant increase in the frequency of each gene transfer was observed. To the best of the authors' knowledge, this is the first study focused on changes in antibiotic resistance associated with a stress response among starter and protective strains. The results suggest that the physicochemical factors prevailing during food production and storage may affect the phenotype of antibiotic resistance and the level of expression of antibiotic resistance genes among microorganisms. As a result, they can contribute to the spread of antibiotic resistance. This points to the need to verify strains used in the food industry for their antibiotic resistance to prevent them from becoming a reservoir for antibiotic resistance genes.202235953184
627870.9997Genome evolution drives transcriptomic and phenotypic adaptation in Pseudomonas aeruginosa during 20 years of infection. The opportunistic pathogen Pseudomonas aeruginosa chronically infects the lungs of patients with cystic fibrosis (CF). During infection the bacteria evolve and adapt to the lung environment. Here we use genomic, transcriptomic and phenotypic approaches to compare multiple isolates of P. aeruginosa collected more than 20 years apart during a chronic infection in a CF patient. Complete genome sequencing of the isolates, using short- and long-read technologies, showed that a genetic bottleneck occurred during infection and was followed by diversification of the bacteria. A 125 kb deletion, an 0.9 Mb inversion and hundreds of smaller mutations occurred during evolution of the bacteria in the lung, with an average rate of 17 mutations per year. Many of the mutated genes are associated with infection or antibiotic resistance. RNA sequencing was used to compare the transcriptomes of an earlier and a later isolate. Substantial reprogramming of the transcriptional network had occurred, affecting multiple genes that contribute to continuing infection. Changes included greatly reduced expression of flagellar machinery and increased expression of genes for nutrient acquisition and biofilm formation, as well as altered expression of a large number of genes of unknown function. Phenotypic studies showed that most later isolates had increased cell adherence and antibiotic resistance, reduced motility, and reduced production of pyoverdine (an iron-scavenging siderophore), consistent with genomic and transcriptomic data. The approach of integrating genomic, transcriptomic and phenotypic analyses reveals, and helps to explain, the plethora of changes that P. aeruginosa undergoes to enable it to adapt to the environment of the CF lung during a chronic infection.202134826267
891980.9997Gene expression in Pseudomonas aeruginosa biofilms. Bacteria often adopt a sessile biofilm lifestyle that is resistant to antimicrobial treatment. Opportunistic pathogenic bacteria like Pseudomonas aeruginosa can develop persistent infections. To gain insights into the differences between free-living P. aeruginosa cells and those in biofilms, and into the mechanisms underlying the resistance of biofilms to antibiotics, we used DNA microarrays. Here we show that, despite the striking differences in lifestyles, only about 1% of genes showed differential expression in the two growth modes; about 0.5% of genes were activated and about 0.5% were repressed in biofilms. Some of the regulated genes are known to affect antibiotic sensitivity of free-living P. aeruginosa. Exposure of biofilms to high levels of the antibiotic tobramycin caused differential expression of 20 genes. We propose that this response is critical for the development of biofilm resistance to tobramycin. Our results show that gene expression in biofilm cells is similar to that in free-living cells but there are a small number of significant differences. Our identification of biofilm-regulated genes points to mechanisms of biofilm resistance to antibiotics.200111677611
472890.9997Antibiotic Resistance Profile, Outer Membrane Proteins, Virulence Factors and Genome Sequence Analysis Reveal Clinical Isolates of Enterobacter Are Potential Pathogens Compared to Environmental Isolates. Outer membrane proteins (OMPs) of gram-negative bacteria play an important role in mediating antibacterial resistance, bacterial virulence and thus affect pathogenic ability of the bacteria. Over the years, prevalence of environmental antibiotic resistant organisms, their transmission to clinics and ability to transfer resistance genes, have been studied extensively. Nevertheless, how successful environmental bacteria can be in establishing as pathogenic bacteria under clinical setting, is less addressed. In the present study, we utilized an integrated approach of investigating the antibiotic resistance profile, presence of outer membrane proteins and virulence factors to understand extent of threat posed due to multidrug resistant environmental Enterobacter isolates. Also, we investigated clinical Enterobacter isolates and compared the results thereof. Results of the study showed that multidrug resistant environmental Enterobacter isolates lacked OmpC, lacked cell invasion abilities and exhibited low reactive oxygen species (ROS) production in neutrophils. In contrast, clinical isolates possessed OmpF, exhibited high invasive and adhesive property and produced higher amounts of ROS in neutrophils. These attributes indicated limited pathogenic potential of environmental Enterobacter isolates. Informations obtained from whole genome sequence of two representative bacterial isolates from environment (DL4.3) and clinical sources (EspIMS6) corroborated well with the observed results. Findings of the present study are significant as it highlights limited fitness of multidrug resistant environmental Enterobacter isolates.202032154188
4306100.9997The correlation study on antimicrobial resistance and biofilm related genes in clinical isolates of Acinetobacter baumannii. In recent years, the proportion of nosocomial infections caused by Acinetobacter baumannii (Ab) strains has increased significantly, and its resistance to antibiotics is rising. The resistance mechanisms of Ab are complex, which include the integron formation, inactivating or deactivating enzyme, outer membrane permeability, biofilm formation, drug exocytosis mechanism and so on. The biofilm formation by bacteria leads to high resistance and immune evasion ability. The aim of this study is to investigate the resistance and distribution patterns of Ab isolates, and the biofilm formation related genes in Ab isolates in our hospital.201324021047
4732110.9997A Comparison of Antibiotics' Resistance Patterns of E. coli and B. subtilis in their Biofilms and Planktonic Forms. BACKGROUND: A biofilm refers to a community of microbial cells that adhere to surfaces that are surrounded by an extracellular polymeric substance. Bacteria employ various defence mechanisms, including biofilm formation, to enhance their survival and resistance against antibiotics. OBJECTIVE: The current study aims to investigate the resistance patterns of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in both biofilms and their planktonic forms. METHODS: E. coli and B. subtilis were used to compare resistance patterns in biofilms versus planktonic forms of bacteria. An antibiotic disc diffusion test was performed to check the resistance pattern of biofilm and planktonic bacteria against different antibiotics such as penicillin G, streptomycin, and ampicillin. Biofilm formation and its validation were done by using quantitative (microtiter plate assay) and qualitative analysis (Congo red agar media). RESULTS: A study of surface-association curves of E. coli and B. subtilis revealed that surface adhesion in biofilms was continuously constant as compared to their planktonic forms, thereby confirming the increased survival of bacteria in biofilms. Also, biofilms have shown high resistance towards the penicillin G, ampicillin and streptomycin as compared to their planktonic form. CONCLUSION: It is safely inferred that E. coli and B. subtilis, in their biofilms, become increasingly resistant to penicillin G, ampicillin and streptomycin.202539092644
4816120.9997Sub-inhibitory concentrations of colistin and imipenem impact the expression of biofilm-associated genes in Acinetobacter baumannii. Acinetobacter baumannii is an opportunistic pathogen that is responsible for nosocomial infections. Imipenem and colistin are drugs that are commonly used to treat severe infections caused by A. baumannii, such as sepsis, ventilator-associated pneumonia, and bacteremia. However, some strains of A. baumannii have become resistant to these drugs, which is a concern for public health. Biofilms produced by A. baumannii increase their resistance to antibiotics and the cells within the inner layers of biofilm are exposed to sub-inhibitory concentrations (sub-MICs) of antibiotics. There is limited information available regarding how the genes of A. baumannii are linked to biofilm formation when the bacteria are exposed to sub-MICs of imipenem and colistin. Thus, this study's objective was to explore this relationship by examining the genes involved in biofilm formation in A. baumannii when exposed to low levels of imipenem and colistin. The study found that exposing an isolate of A. baumannii to low levels of these drugs caused changes in their drug susceptibility pattern. The relative gene expression profiles of the biofilm-associated genes exhibited a change in their expression profile during short-term and long-term exposure. This study highlights the potential consequences of overuse and misuse of antibiotics, which can help bacteria become resistant to these drugs.202438489041
4404130.9997Adaptation to Biocides Cetrimide and Chlorhexidine in Bacteria from Organic Foods: Association with Tolerance to Other Antimicrobials and Physical Stresses. Chlorhexidine (CH) and quaternary ammonium compounds (QAC), such as cetrimide (CE), are widely used as disinfectants because of their broad antimicrobial spectrum. However, their frequent use for disinfection in different settings may promote bacterial drug resistance against both biocides and clinically relevant antibiotics. This study analyzes the effects of stepwise exposure to cetrimide (CE) and chlorhexidine (CH) of bacteria from organic foods and previously classified as biocide-sensitive. Gradual exposure of these strains to biocides resulted in mainly transient decreased antimicrobial susceptibility to other antibiotics and to biocides. Biocide-adapted bacteria also exhibit alterations in physiological characteristics, mainly decreased heat tolerance, or gastric acid tolerance in CE-adapted strains, while bile resistance does not seem to be influenced by biocide adaptation. Results from this study suggest that changes in membrane fluidity may be the main mechanism responsible for the acquisition of stable tolerance to biocides.201728177232
4703140.9997Positive adaptive state: microarray evaluation of gene expression in Salmonella enterica Typhimurium exposed to nalidixic acid. The emergence of antimicrobial resistance among foodborne bacteria associated with food animal production is an important global issue. We hypothesised that antibiotics generate a positive adaptive state in Salmonella that actively contributes to the development of antimicrobial resistance. This is opposed to common views that antimicrobials only act as a passive selective pressure. Microarray analysis was used to evaluate changes in gene expression that occur upon exposure of Salmonella enterica Typhimurium ATCC 14028 to 1.6 microg/mL of nalidixic acid. The results showed a significant (P < 0.02) difference (fold expression differences >2.0) in the expression of 226 genes. Comparatively repressed transcripts included Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Induced genes included efflux pumps representing all five families of multidrug-resistance efflux pumps, outer membrane lipoproteins, and genes involved in regulating lipopolysaccharide chain length. This profile suggests both enhanced antimicrobial export from the cell and membrane permeability adaptations to limit diffusion of nalidixic acid into the cell. Finally, increased expression of the error-prone DNA repair mechanisms were also observed. From these data we show a highly integrated genetic response to nalidixic acid that places Salmonella into a positive adaptive state that elicits mutations. Evaluation of gene expression profile changes that occur during exposure to antibiotics will continue to improve our understanding of the development of antibiotic resistance.200717600486
6329150.9997Autoinducer-2 influences tetracycline resistance in Streptococcus suis by regulating the tet(M) gene via transposon Tn916. The concern over increasing resistance to tetracyclines (TCs), such as tetracycline and chlortetracycline, necessitates exploration of new approaches to combating infection in antimicrobial therapy. Given that bacteria use the chemical language of autoinducer 2 (AI-2) signaling molecules in order to communicate and regulate group behaviors, we asked whether the AI-2 signaling influence the tetracyclines antibiotics susceptibility in S. suis. Our present work demonstrated that MIC increased when exogenous AI-2 was added, when compared to the wild type strain. When grown in the presence of sub-MIC of antibiotics, it has been shown that exogenous AI-2 increases growth rate and biofilm formation. These results suggest that the TCs resistance in S. suis could involve a signaling mechanism. Base on the above observations, transcriptomic analyses showed significant differences in the expression of tet(M) of tetracyclines resistance genes, as well as differences in Tn916 transposon related genes transcription, as judged by RT-PCR. Our results provide strong evidence that AI-2 signaling molecules is may involve in TCs antibiotic resistance in S. suis by regulating tet(M) gene via Tn916 transposon. This study may suggest that targeting AI-2 signaling in bacteria could represent an alternative approach in antimicrobial therapy.202031837515
6293160.9997Gentamicin resistance to Escherichia coli related to fatty acid metabolism based on transcriptome analysis. Antibiotic overuse and misuse have promoted the emergence and spread of antibiotic-resistant bacteria. Increasing bacterial resistance to antibiotics is a major healthcare problem, necessitating elucidation of antibiotic resistance mechanisms. In this study, we explored the mechanism of gentamicin resistance by comparing the transcriptomes of antibiotic-sensitive and -resistant Escherichia coli. A total of 410 differentially expressed genes were identified, of which 233 (56.83%) were up-regulated and 177 (43.17%) were down-regulated in the resistant strain compared with the sensitive strain. Gene Ontology (GO) analysis classifies differential gene expression into three main categories: biological processes, cellular components, and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the up-regulated genes were enriched in eight metabolic pathways, including fatty acid metabolism, which suggests that fatty acid metabolism may be involved in the development of gentamicin resistance in E. coli. This was demonstrated by measuring the acetyl-CoA carboxylase activity, plays a fundamental role in fatty acid metabolism, was increased in gentamicin-resistant E. coli. Treatment of fatty acid synthesis inhibitor, triclosan, promoted gentamicin-mediated killing efficacy to antibiotic-resistant bacteria. We also found that exogenous addition of oleic acid, which involved in fatty acid metabolism, reduced E. coli sensitivity to gentamicin. Overall, our results provide insight into the molecular mechanism of gentamicin resistance development in E. coli.202337224563
3806170.9997Bioinformatic analysis reveals the association between bacterial morphology and antibiotic resistance using light microscopy with deep learning. Although it is well known that the morphology of Gram-negative rods changes on exposure to antibiotics, the morphology of antibiotic-resistant bacteria in the absence of antibiotics has not been widely investigated. Here, we studied the morphologies of 10 antibiotic-resistant strains of Escherichia coli and used bioinformatics tools to classify the resistant cells under light microscopy in the absence of antibiotics. The antibiotic-resistant strains showed differences in morphology from the sensitive parental strain, and the differences were most prominent in the quinolone-and β-lactam-resistant bacteria. A cluster analysis revealed increased proportions of fatter or shorter cells in the antibiotic-resistant strains. A correlation analysis of morphological features and gene expression suggested that genes related to energy metabolism and antibiotic resistance were highly correlated with the morphological characteristics of the resistant strains. Our newly proposed deep learning method for single-cell classification achieved a high level of performance in classifying quinolone-and β-lactam-resistant strains.202439364166
9922180.9997De novo acquisition of antibiotic resistance in six species of bacteria. Bacteria can become resistant to antibiotics in two ways: by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole-genome sequencing at two time points of the evolutionary trajectory. In this study, we found that (1) all of the six strains can develop high levels of resistance against most antibiotics; (2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination; (3) the number of mutations varies widely, with Y. enterocolitica having by far the most; (4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species; and (5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes. The outcome of this study may assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.IMPORTANCEMost studies on de novo development of antimicrobial resistance have been performed on Escherichia coli. To examine whether the conclusions of this research can be applied to more bacterial species, six species of veterinary importance were made resistant to six antibiotics, each of a different class. The rapid build-up of resistance observed in all six species upon exposure to non-lethal concentrations of antimicrobials indicates a similar ability to adjust to the presence of antibiotics. The large differences in the number of DNA mutations accompanying de novo resistance suggest that the mechanisms and pathways involved may differ. Hence, very similar phenotypes can be the result of various genotypes. The implications of the outcome are to be considered by policymakers in the area of veterinary and human healthcare.202539907470
6333190.9997Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda. Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication.201728210241