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      Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria

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          Abstract

          <p class="first" id="d1569777e174">Gram-negative microorganisms are a significant cause of infection in both community and nosocomial settings. The increase, emergence, and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. One of the mechanisms of resistance used by bacteria is biofilm formation, which is also a mechanism of virulence. This study analyzed the possible relationship between antimicrobial resistance and biofilm formation among isolates of three Gram-negative bacteria species. Several relationships were found between the ability to form biofilm and antimicrobial resistance, being different for each species. Indeed, gentamicin and ceftazidime resistance was related to biofilm formation in Escherichia coli, piperacillin/tazobactam, and colistin in Klebsiella pneumoniae, and ciprofloxacin in Pseudomonas aeruginosa. However, no relationship was observed between global resistance or multidrug-resistance and biofilm formation. In addition, compared with other reported data, the isolates in the present study showed higher rates of antimicrobial resistance. In conclusion, the acquisition of specific antimicrobial resistance can compromise or enhance biofilm formation in several species of Gram-negative bacteria. However, multidrug-resistant isolates do not show a trend to being greater biofilm producers than non-multiresistant isolates. </p>

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          Aminoglycoside antibiotics induce bacterial biofilm formation.

          Biofilms are adherent aggregates of bacterial cells that form on biotic and abiotic surfaces, including human tissues. Biofilms resist antibiotic treatment and contribute to bacterial persistence in chronic infections. Hence, the elucidation of the mechanisms by which biofilms are formed may assist in the treatment of chronic infections, such as Pseudomonas aeruginosa in the airways of patients with cystic fibrosis. Here we show that subinhibitory concentrations of aminoglycoside antibiotics induce biofilm formation in P. aeruginosa and Escherichia coli. In P. aeruginosa, a gene, which we designated aminoglycoside response regulator (arr), was essential for this induction and contributed to biofilm-specific aminoglycoside resistance. The arr gene is predicted to encode an inner-membrane phosphodiesterase whose substrate is cyclic di-guanosine monophosphate (c-di-GMP)-a bacterial second messenger that regulates cell surface adhesiveness. We found that membranes from arr mutants had diminished c-di-GMP phosphodiesterase activity, and P. aeruginosa cells with a mutation changing a predicted catalytic residue of Arr were defective in their biofilm response to tobramycin. Furthermore, tobramycin-inducible biofilm formation was inhibited by exogenous GTP, which is known to inhibit c-di-GMP phosphodiesterase activity. Our results demonstrate that biofilm formation can be a specific, defensive reaction to the presence of antibiotics, and indicate that the molecular basis of this response includes alterations in the level of c-di-GMP.
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            Antibiotic-induced biofilm formation.

            Surface-attached colonies of bacteria known as biofilms play a major role in the pathogenesis of device-related infections. Biofilm colonies are notorious for their resistance to suprainhibitory concentrations of antibiotics. Numerous studies have shown that subminimal inhibitory concentrations of some antibiotics can act as agonists of bacterial biofilm formation in vitro, a process that may have clinical relevance. This article reviews studies demonstrating that low-dose antibiotics induce bacterial biofilm formation. These studies have provided important information about the regulation of biofilm formation and the signaling pathways involved in global gene regulation in response to cell stressors. It is still unclear whether antibiotic-induced biofilm formation contributes to the inconsistent success of antimicrobial therapy for device infections.
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              Relationship between Antibiotic Resistance, Biofilm Formation, and Biofilm-Specific Resistance in Acinetobacter baumannii

              In this study, we aimed to examine the relationships between antibiotic resistance, biofilm formation, and biofilm-specific resistance in clinical isolates of Acinetobacter baumannii. The tested 272 isolates were collected from several hospitals in China during 2010–2013. Biofilm-forming capacities were evaluated using the crystal violet staining method. Antibiotic resistance/susceptibility profiles to 21 antibiotics were assessed using VITEK 2 system, broth microdilution method or the Kirby-Bauer disc diffusion method. The minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) to cefotaxime, imipenem, and ciprofloxacin were evaluated using micro dilution assays. Genetic relatedness of the isolates was also analyzed by pulsed-field gel electrophoresis (PFGE) and plasmid profile. Among all the 272 isolates, 31 were multidrug-resistant (MDR), and 166 were extensively drug-resistant (XDR). PFGE typing revealed 167 pattern types and 103 clusters with a similarity of 80%. MDR and XDR isolates built up the main prevalent genotypes. Most of the non-MDR isolates were distributed in a scattered pattern. Additionally, 249 isolates exhibited biofilm formation, among which 63 were stronger biofilm formers than type strain ATCC19606. Population that exhibited more robust biofilm formation likely contained larger proportion of non-MDR isolates. Isolates with higher level of resistance tended to form weaker biofilms. The MBECs for cefotaxime, imipenem, and ciprofloxacin showed a positive correlation with corresponding MICs, while the enhancement in resistance occurred independent of the quantity of biofilm biomass produced. Results from this study imply that biofilm acts as a mechanism for bacteria to get a better survival, especially in isolates with resistance level not high enough. Moreover, even though biofilms formed by isolates with high level of resistance are always weak, they could still provide similar level of protection for the isolates. Further explorations genetically would improve our understanding of these processes and provide novel insights in the therapeutics and prevention against A. baumannii biofilm-related infections.
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                Author and article information

                Journal
                Microbial Drug Resistance
                Microbial Drug Resistance
                Mary Ann Liebert Inc
                1076-6294
                1931-8448
                January 2019
                January 2019
                : 25
                : 1
                : 72-79
                Affiliations
                [1 ]ISGlobal, Barcelona Center for International Health Research (CRESIB), Hospital Clínic—Universitat de Barcelona, Barcelona, Spain.
                [2 ]Department of Microbiology, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
                [3 ]CIBERes (CIBER de Enfermedades Respiratorias), ISCIII, Madrid, Spain.
                [4 ]Department of Microbiology, Hospital Mutua de Terrassa, Terrassa, Spain.
                [5 ]Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.
                [6 ]Department of Microbiology, Hospital Clínic—Universitat de Barcelona, Barcelona, Spain.
                Article
                10.1089/mdr.2018.0027
                30142035
                4b63e91f-b8ab-412c-b370-d6a252c425f0
                © 2019

                https://www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/

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