Effect of sub-lethal chemical disinfection on the biofilm forming ability, resistance to antibiotics and expression of virulence genes of Salmonella Enteritidis biofilm-surviving cells. - Related Documents




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894801.0000Effect of sub-lethal chemical disinfection on the biofilm forming ability, resistance to antibiotics and expression of virulence genes of Salmonella Enteritidis biofilm-surviving cells. Although disinfection procedures are widely implemented in food environments, bacteria can survive and present increased virulence/resistance. Since little is known about these phenomena regarding biofilms, this study aimed to investigate the effect of chemical disinfection on biofilm-derived cells of Salmonella Enteritidis. Using a reference strain (NCTC 13349) and a food isolate (350), biofilm susceptibility to benzalkonium chloride (BAC), sodium hypochlorite (SH) and hydrogen peroxide (HP) was evaluated and biofilms were exposed to sub-lethal concentrations of each disinfectant. Biofilm-derived cells were characterized for their biofilm forming ability, antibiotic resistance and expression of virulence-associated genes. Except for a few instances, disinfectant exposure did not alter antibiotic susceptibility. However, SH and HP exposure enhanced the biofilm forming ability of Salmonella Enteritidis NCTC 13349. After BAC and HP exposure, biofilm-derived cells presented a down-regulation of rpoS. Exposure to BAC also revealed an up-regulation of invA, avrA and csgD on Salmonella Enteritidis NCTC 13349. The results obtained suggest that biofilm-derived cells that survive disinfection may represent an increased health risk.202031997643
629410.9996Comparison of Gene Expression Profiles of Uropathogenic Escherichia Coli CFT073 after Prolonged Exposure to Subinhibitory Concentrations of Different Biocides. Biocides are chemical compounds widely used for sterilization and disinfection. The aim of this study was to examine whether exposure to subinhibitory biocide concentrations influenced transcriptional expression of genes that could improve a pathogen's drug resistance or fitness. We used DNA microarrays to investigate the transcriptome of the uropathogenic Escherichia coli strain CFT073 in response to prolonged exposure to subinhibitory concentrations of four biocides: benzalkonium chloride, chlorhexidine, hydrogen peroxide and triclosan. Transcription of a gene involved in polymyxin resistance, arnT, was increased after treatment with benzalkonium chloride. However, pretreatment of the bacteria with this biocide did not result in cross-resistance to polymyxin in vitro. Genes encoding products related to transport formed the functional group that was most affected by biocides, as 110 out of 884 genes in this category displayed altered transcription. Transcripts of genes involved in cysteine uptake, sulfate assimilation, dipeptide transport, as well as cryptic phage genes were also more abundant in response to several biocides. Additionally, we identified groups of genes with transcription changes unique to single biocides that might include potential targets for the biocides. The biocides did not increase the resistance potential of the pathogen to other antimicrobials.201931569631
894720.9996Response and Formation Mechanism of Highly Antibiotic-Resistant Dormant Subpopulations in Bioaerosol during Aerosolizing from Aquatic Environments. The characteristics and responses of bacteria aerosolized from aquatic to atmospheric environments are poorly understood. In this study, three antibiotic-resistant bacteria (cefotaxime (CTX)-resistant, polymyxin B (MCR)-resistant, and gentamycin (GEN)-resistant Escherichia coli DH5α) were used to explore microbial aerosolization responses and mechanisms. E. coli bioaerosols had improved resistance to aerosolizing stress through carrying antibiotic resistance genes, developing different phenotype distributions, including wild-type, small colony variant (SCV), and viable but nonculturable (VBNC) subpopulations. E. coli DH5α (CTX) bioaerosols showed the highest percentage of VBNCs (15.1%), while those E. coli DH5α (GEN) bioaerosols showed the highest percentage of SCVs (13.4%). A consistent variation of reduced growth and metabolic activity but increased ATP accumulation and ROS content was observed across SCVs of all strains. Notably, the SCVs of GEN-resistant E. coli exhibited the most pronounced ATP accumulation and a significant upregulation of protein synthesis genes. Collectively, oxidative stress responses were activated to defend against stress in E. coli bioaerosols and promoted the formation of dormant subpopulations (SCV and VBNC). However, a divergent mechanistic was observed: up-regulation of cell wall synthesis genes promoted VBNC formation, while up-regulation of protein synthesis genes promoted SCV formation. These findings highlight that antibiotic resistance in aquatic bacteria contributes to the formation of different dormant subpopulations in bioaerosols that pose different risks to ecosystems and human health.202541073078
675430.9996Real-time PCR based analysis of metal resistance genes in metal resistant Pseudomonas aeruginosa strain J007. A uranium (U)-resistant and -accumulating Pseudomonas aeruginosa strain was characterized to assess the response of toxic metals toward its growth and expression of metal resistance determinants. The bacterium showed MIC (minimum inhibitory concentration) values of 6, 3, and 2 mM for Zn, Cu, and Cd, respectively; with resistance phenotype conferred by periplasmic Cu sequestering copA and RND type heavy metal efflux czcA genes. Real-time PCR-based expression analysis revealed significant upregulation of both these genes upon exposure to low concentrations of metals for short duration, whereas the global stress response gene sodA encoding superoxide dismutase enzyme was upregulated only at higher metal concentrations or longer exposure time. It could also be inferred that copA and czcA are involved in providing resistance only at low metal concentrations, whereas involvement of "global stress response" phenomenon (expression of sodA) at higher metal concentration or increased exposure was evident. This study provides significant understanding of the adaptive response of bacteria surviving in metal and radionuclide contaminated environments along with the development of real-time PCR-based quantification method of using metal resistance genes as biomarker for monitoring relevant bacteria in such habitats.201626662317
895440.9996Effect 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
629750.9996Combined effect of bacteriophage and antibiotic on the inhibition of the development of antibiotic resistance in Salmonella typhimurium. This study was designed to evaluate the combined effects of bacteriophage and antibiotic on the reduction of the development of antibiotic-resistance in Salmonella typhimurium LT2. The susceptibilities of S. typhimurium to ciprofloxacin and erythromycin were increased when treated with bacteriophages, showing more than 10% increase in clear zone sizes and greater than twofold decrease in minimum inhibitory concentration values. The growth of S. typhimurium was effectively inhibited by the combination of bacteriophage P22 and ciprofloxacin. The combination treatment effectively reduced the development of antibiotic resistance in S. typhimurium. The relative expression levels of efflux pump-related genes (acrA, acrB, and tolC) and outer membrane-related genes (ompC, ompD, and ompF) were decreased at all treatments. This study provides useful information for designing new antibiotic therapy to control antibiotic-resistant bacteria.201830263855
895560.9996Increasing resistance of planktonic and biofilm cultures of Burkholderia cepacia to ciprofloxacin and ceftazidime during exponential growth. The change in resistance of Burkholderia cepacia to ceftazidime and to ciprofloxacin during the exponential phase and up to the onset of stationary phase was assessed along the growth curve in batch culture. B. cepacia was grown in planktonic culture and in a biofilm on a membrane support. Resistance increased progressively during the exponential phase, being increased by ten-fold about every four generations. Bacteria grown in a biofilm were about 15 times more resistant than equivalent planktonic-grown bacteria. The growth rate was not the key factor for the development of resistance. The growth phase and the mode of growth have a fundamental impact on the susceptibility of B. cepacia towards antimicrobial agents. Bacteria growing at the same rate may differ greatly in their resistance to antimicrobial agents.19989738832
629270.9995Genome-Wide Screening and Characterization of Genes Involved in Response to High Dose of Ciprofloxacin in Escherichia coli. The global emergence of antibiotic resistance, especially in Gram-negative bacteria, is an urgent threat to public health. Inevitably, considering its extensive use and misuse, resistance toward ciprofloxacin has increased in almost all clinically relevant bacteria. This study aimed to investigate the transcriptome changes at a high concentration of ciprofloxacin in Escherichia coli. In brief, 1,418 differentially expressed genes (DEGs) were identified, from which 773 genes were upregulated by ciprofloxacin, whereas 651 genes were downregulated. Enriched biological pathways reflected the upregulation of biological processes such as DNA damage and repair system, toxin/antitoxin systems, formaldehyde detoxification system. With kyoto encyclopedia of genes and genomes pathway analysis, higher expressed DEGs were associated with "LPS biosynthesis," "streptomycin biosynthesis," and "polyketide sugar unit biosynthesis." Lower expressed DEGs were associated with "biosynthesis of amino acids" and "flagellar assembly" pathways. After treatment of ciprofloxacin, lipopolysaccharide (LPS) release was increased by two times, and the gene expression level of LPS synthesis was elevated (p < 0.05) in both reference and clinical strains. Our results demonstrated that transient exposure to high-dose ciprofloxacin is a double-edged sword. Cautions should be taken when administering high-dose antibiotic treatment for infectious diseases.202235512736
675080.9995Viable but non-culturable E. coli induced by low level chlorination have higher persistence to antibiotics than their culturable counterparts. Disinfectant used in drinking water treatment and distribution system can induce culturable bacteria, including various kinds of pathogenic bacteria, into viable but non-culturable (VBNC) state. The loss of cultural state, resuscitation and environmental persistence of VBNC bacteria will severely damage drinking water microbiological safety and thus pose a risk to public health. The manner in which chlorination treatment induced a VBNC state in Escherichia coli and the antibiotic persistence of VBNC bacteria was investigated. It was found that low dosage of chlorine (0.5 mg L(-1)) disinfection effectively reduced the culturability of E. coli and induced a VBNC state, after which metabolic activity was reduced and persistence to 9 typical antibiotics was enhanced. Furthermore, RT-qPCR results showed that stress resistance genes (rpoS, marA, ygfA, relE) and ARGs, especially efflux genes were up-regulated compared with culturable cells. The intracellular concentration was tested and found to be lower in VBNC cells than in actively growing E. coli, which suggested a higher efflux rate. The data presented indicate that VBNC E. coli are more persistent than culturable counterparts to a wide variety of antibiotics. VBNC E. coli constitute a potential source of contamination and should be considered during monitoring of drinking water networks.201728662489
895690.9995Biofilm characteristics and transcriptomic profiling of Acinetobacter johnsonii defines signatures for planktonic and biofilm cells. Most bacteria in the natural environment have a biofilm mode of life, which is intrinsically tolerant to antibiotics. While until now, the knowledge of biofilm formation by Acinetobacter johnsonii is not well understood. In this study, the characteristics and the effect of a sub-inhibitory concentration of antibiotic on A. johnsonii biofilm and planktonic cells were determined. We discovered a positive relationship between biofilm formation and tetracycline resistance, and biofilms rapidly evolve resistance to tetracycline they are treated with. Persister cells commonly exist in both planktonic and biofilm cells, with a higher frequency in the latter. Further transcriptomic analysis speculates that the overexpression of multidrug resistance genes and stress genes were mainly answered to sub lethal concentration of tetracycline in planktonic cells, and the lower metabolic levels after biofilm formation result in high resistance level of biofilm cells to tetracycline. Altogether, these data suggest that A. johnsonii can adjust its phenotype when grown as biofilm and change its metabolism under antibiotic stress, and provide implications for subsequent biofilm control.202235718162
6755100.9995Impact of lead (Pb(2+)) on the growth and biological activity of Serratia marcescens selected for wastewater treatment and identification of its zntR gene-a metal efflux regulator. Microorganisms isolated from contaminated areas play an important role in bioremediation processes. They promote heavy metal removal from the environment by adsorbing ions onto the cell wall surface, accumulating them inside the cells, or reducing, complexing, or precipitating these substances in the environment. Microorganism-based bioremediation processes can be highly efficient, low-cost and have low environmental impact. Thus, the present study aimed to select Pb(2+)-resistant bacteria and evaluate the growth rate, biological activity, and the presence of genes associated with metal resistance. Serratia marcescens CCMA 1010, that was previously isolated from coffee processing wastewater, was selected since was able to growth in Pb(2+) concentrations of up to 4.0 mM. The growth rate and generation time did not differ from those of the control (without Pb(2+)), although biological activity decreased in the first hour of exposure to these ions and stabilized after this period. The presence of the zntR, zntA and pbrA genes was analysed, and only zntR was detected. The zntR gene encodes a protein responsible for regulating the production of ZntA, a transmembrane protein that facilitates Pb(2+) extrusion out of the cell. S. marcescens CCMA 1010 demonstrated a potential for use as bioindicator that has potential to be used in bioremediation processes due to its resistance to high concentrations of Pb(2+), ability to grow until 24 h of exposure, and possession of a gene that indicates the existence of mechanisms associated with resistance to lead (Pb(2+)).202336752862
6295110.9995Anaerobiosis and Mutations Can Reduce Susceptibility of Pseudomonas aeruginosa to Tobramycin Without Reducing the Cellular Concentration of the Antibiotic. Chronic infections of Pseudomonas aeruginosa are commonly treated with tobramycin. During infections, the bacteria can exist under conditions of oxygen deprivation that render them less susceptible to this antibiotic. The aims of this research were to investigate the genetic basis of tobramycin resistance under anaerobic conditions, and to investigate the effects of anaerobiosis and mutations on the cellular concentration of tobramycin. Ten mutants with lowered susceptibility to tobramycin than wild-type bacteria were evolved from a laboratory reference strain under anaerobic conditions. Mutations were identified by genome sequencing. Mutations had arisen most frequently in the fusA1 gene that encodes elongation factor EF-G1A and in genes involved in twitching motility. Cellular concentrations of tobramycin were then measured. Mutations in fusA1 or absence of the MexXY efflux pump that is associated with tobramycin resistance did not alter the cellular tobramycin concentration under either anaerobic or aerobic conditions. Anaerobic growth reduced the cellular concentration of tobramycin, relative to aerobically grown bacteria, in some but not all of five tested P. aeruginosa isolates. Overall, our findings indicate that anaerobiosis and mutations that reduce aminoglycoside effectiveness do not lower the cellular concentration of antibiotic but instead reduce susceptibility through other mechanisms.202540005562
8984120.9995Environmental peracetic acid increases antibiotic resistance in Streptococcus Suis. Disinfectants in the environment have important impacts on the occurrence of antibiotic resistant bacteria, posing a new threat to public health. Streptococcus suis (S. suis) can survive in the environment for three months and carries antibiotic resistance genes. However, it remains unclear whether disinfectants directly induce antibiotic resistance in S. suis. Here, we conducted induction experiments on the S. suis standard strain (CVCC609) with eight disinfectants at different concentrations and investigated their effects on the antibiotic resistance mechanism of S. suis. The results showed that only 64 mg L(-1) peracetic acid (PAA) led to an increase (8-fold) in S. suis resistance to tiamulin (TIA) with genetic stability. The treatment also induced significant changes in the morphology and capsule of the mutant strains, as well as triggered an increase in reactive oxygen species and biofilms in bacterial cells, resulting in an emergency response. Moreover, PAA significantly decreased the cell membrane permeability and led to slight changes in the adenosine triphosphate level. The key differentially expressed genes are closely related to these resistance mechanisms. These results reveal the co-selection mechanism of S. suis resistance to PAA and TIA, and highlight the importance of standardized application of disinfectants in livestock and poultry farming.202540286665
8919130.9995Gene 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
8957140.9995Transcriptome Profiling Reveals Interplay of Multifaceted Stress Response in Escherichia coli on Exposure to Glutathione and Ciprofloxacin. We have previously reported that supplementation of exogenous glutathione (GSH) promotes ciprofloxacin resistance in Escherichia coli by neutralizing antibiotic-induced oxidative stress and by enhancing the efflux of antibiotic. In the present study, we used a whole-genome microarray as a tool to analyze the system-level transcriptomic changes of E. coli on exposure to GSH and/or ciprofloxacin. The microarray data revealed that GSH supplementation affects redox function, transport, acid shock, and virulence genes of E. coli. The data further highlighted the interplay of multiple underlying stress response pathways (including those associated with the genes mentioned above and DNA damage repair genes) at the core of GSH, offsetting the effect of ciprofloxacin in E. coli. The results of a large-scale validation of the transcriptomic data using reverse transcription-quantitative PCR (RT-qPCR) analysis for 40 different genes were mostly in agreement with the microarray results. The altered growth profiles of 12 different E. coli strains carrying deletions in the specific genes mentioned above with GSH and/or ciprofloxacin supplementation implicate these genes in the GSH-mediated phenotype not only at the molecular level but also at the functional level. We further associated GSH supplementation with increased acid shock survival of E. coli on the basis of our transcriptomic data. Taking the data together, it can be concluded that GSH supplementation influences the expression of genes of multiple stress response pathways apart from its effect(s) at the physiological level to counter the action of ciprofloxacin in E. coli. IMPORTANCE The emergence and spread of multidrug-resistant bacterial strains have serious medical and clinical consequences. In addition, the rate of discovery of new therapeutic antibiotics has been inadequate in last few decades. Fluoroquinolone antibiotics such as ciprofloxacin represent a precious therapeutic resource in the fight against bacterial pathogens. However, these antibiotics have been gradually losing their appeal due to the emergence and buildup of resistance to them. In this report, we shed light on the genome-level expression changes in bacteria with respect to glutathione (GSH) exposure which act as a trigger for fluoroquinolone antibiotic resistance. The knowledge about different bacterial stress response pathways under conditions of exposure to the conditions described above and potential points of cross talk between them could help us in understanding and formulating the conditions under which buildup and spread of antibiotic resistance could be minimized. Our findings are also relevant because GSH-induced genome-level expression changes have not been reported previously for E. coli.201829468195
6746150.9995Environmental concentration of the quaternary ammonium disinfectant benzalkonium chloride strongly induces resistance gene profiles in fish. Disinfectants are non-antibiotic biocides that have been used extensively in daily life, particularly since the onset of the COVID-19 pandemic. However, their effect on drug resistance has not received sufficient attention. Here, marine medaka were subjected to an environmental concentration (10 μg/L) of benzalkonium chloride (BAC), sulfamethazine (SMZ), and their combination, aiming to elucidate their contributions to antibiotic resistance. Overall, 10 μg/L BAC exhibited a stronger induction potential for multiple antibiotic resistance genes (ARGs) relative to a similar level of SMZ. Specifically, tetracycline resistance genes were readily induced, regardless of exposure to BAC, SMZ, or their combination. BAC exhibited a more pronounced induction of ARGs than SMZ and showed a stronger potential to stimulate multidrug resistance. SMZ and BAC induced distinct virulence factors. Bacteria increased pathogenicity primarily through biofilm formation and enhanced community sensing under SMZ exposure, whereas iron acquisition and the production of reactive oxygen species appeared to be the main mechanisms by which bacteria evaded host defenses under BAC exposure. A greater number of ARGs demonstrated a significant positive correlation with virulence factors following BAC exposure compared to both the SMZ exposure group and the co-exposure group, which further confirmed the strong ability of BAC to induce multidrug resistance. In summary, owing to the typically unregulated and low-dose use of disinfectants in daily life and their pseudo-persistence in the environment, their potential to induce resistance may exceed that of antibiotics. Therefore, increased attention and preventive measures are required to address their resistance-inducing effects.202540073566
6747160.9995Tetracycline accumulation in biofilms enhances the selection pressure on Escherichia coli for expression of antibiotic resistance. Microorganisms are present as either biofilm or planktonic species in natural and engineered environments. Little is known about the selection pressure emanating from exposure to sub-minimal inhibitory concentration of antibiotics on planktonic vs. biofilm bacteria. In this study, an E. coli bioreporter was used to develop biofilms on glass and high-density polyethylene (HDPE) surfaces, and compared with the corresponding planktonic bacteria in antibiotic resistance expression when exposed to a range of μg/L levels of tetracycline. The antibiotic resistance-associated fluorescence emissions from biofilm E. coli reached up to 1.6 times more than those from planktonic bacteria. The intensively developed biofilms on glass surfaces caused the embedded bacteria to experience higher selection pressure and express more antibiotic resistance than those on HDPE surfaces. The temporal pattern of fluorescence emissions from biofilm E. coli was consistent with the biofilm-developing processes during the experimental period. The increased expression of antibiotic resistance from biofilm bacteria could be attributed to the high affinity of tetracycline with extracellular polymeric substances (EPS). The enhanced accumulation of tetracycline in biofilms could exert higher selection pressure on the embedded bacteria. These results suggest that in many natural and engineered systems the higher antibiotic resistance in biofilm bacteria could be attributed partially to the retention antibiotics by the EPS in biofilms.202336252660
6298170.9995Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem. Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectants, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic and transcriptomic changes caused by disinfectant exposure in Gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from the exposure of Gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of Gram-negative bacteria in increasingly higher subMICs of the NaOCl disinfectant were sufficient to increase the MIC to >2500 µg/mL NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after the exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (p < 0.01). An investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1250 µg/mL of NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to the increased expression of resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.202439335002
6330180.9995Transcriptomic study of ciprofloxacin resistance in Streptomyces coelicolor A3(2). Soil organisms exhibit resistance to a wide range of antibiotics as they either need to protect themselves from endogenous antibiotics or from those present in their soil environment. The soil could serve as a reservoir for resistance mechanisms that have already emerged or have the potential to emerge in clinically important bacteria. Streptomyces coelicolor, a non-pathogenic soil-dwelling organism, is thus used as a model for the study of intrinsic resistance. Preliminary screening of several compounds showed that S. coelicolor had high intrinsic resistance for the fluoroquinolone group of antibiotics. We subjected the bacteria to sub-inhibitory concentrations of ciprofloxacin and studied the transcriptomic response using microarrays. The data were supported with various biochemical and phenotypic assays. Ciprofloxacin treatment leads to differential expression of many genes with enhanced mRNA expression of its target, DNA gyrase gene. High induction of DNA repair pathways was also observed and many transporters were upregulated. Ciprofloxacin was found to induce ROS formation in a dose dependent manner. Reduction of ROS via anti-oxidants increased the effective MIC of the drug in the bacteria. The regulation of antibiotic resistance in S. coelicolor was studied systematically and contribution of different mechanisms in the development of resistance was assessed. Our data suggest that multiple mechanisms work in coordination to facilitate the cell to combat the stress due to ciprofloxacin.201324100886
6329190.9995Autoinducer-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