Gene interaction network approach to elucidate the multidrug resistance mechanisms in the pathogenic bacterial strain Proteus mirabilis

Proteus mirabilis is one among the most frequently identified pathogen in patients with the urinary tract infection. The multidrug resistance exhibited by P. mirabilis renders the treatment ineffective, and new progressive strategies are needed to overcome the antibiotic resistance (AR). We have analyzed the evolutionary relationship of 29 P. mirabilis strains available in the National Center for Biotechnology Information‐Genome database. The antimicrobial resistance genes of P. mirabilis along with the enriched pathways and the Gene Ontology terms are analyzed using gene networks to understand the molecular basis of AR. The genes rpoB, tufB, rpsl, fusA, and rpoA could be exploited as potential drug targets as they are involved in regulating the vital functions within the bacterium. The drug targets reported in the present study will aid researchers in developing new strategies to combat multidrug‐resistant P. mirabilis.

[1]  Serge Morand,et al.  Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria , 2014, Front. Microbiol..

[2]  S. Rasmussen,et al.  Identification of acquired antimicrobial resistance genes , 2012, The Journal of antimicrobial chemotherapy.

[3]  Sudha Ramaiah,et al.  Network and Polymorphic Analysis of Obesity Candidate Gene-Plin 1 : A Bioinformatics Approach , 2015 .

[4]  Sudha Ramaiah,et al.  Network and Polymorphic Analysis of Obesity Candidate Gene-Plin1: A Bioinformatics Approach , 2014 .

[5]  David A. Bader,et al.  Approximating Betweenness Centrality , 2007, WAW.

[6]  Brian D. Ondov,et al.  The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes , 2014, Genome Biology.

[7]  C. Bourne.  Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial Discovery , 2014, Antibiotics.

[8]  Colin Cooper,et al.  Algorithms and Models for the Web-Graph , 2004, Lecture Notes in Computer Science.

[9]  M. Khurshid,et al.  Characteristics and Antibiotic Resistance of Urinary Tract Pathogens Isolated From Punjab, Pakistan , 2015, Jundishapur journal of microbiology.

[10]  P. Coll,et al.  Increase in beta-lactam-resistant Proteus mirabilis strains due to CTX-M- and CMY-type as well as new VEB- and inhibitor-resistant TEM-type beta-lactamases. , 2008, The Journal of antimicrobial chemotherapy.

[11]  Rida Assaf,et al.  Improvements to PATRIC, the all-bacterial Bioinformatics Database and Analysis Resource Center , 2016, Nucleic Acids Res..

[12]  Fidel Ramírez,et al.  Computing topological parameters of biological networks , 2008, Bioinform..

[13]  Anand Anbarasu,et al.  Gene Network Analysis of Metallo Beta Lactamase Family Proteins Indicates the Role of Gene Partners in Antibiotic Resistance and Reveals Important Drug Targets , 2016, Journal of cellular biochemistry.

[14]  Damian Szklarczyk,et al.  The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored , 2010, Nucleic Acids Res..

[15]  Henry D. Isenberg,et al.  Manual of Clinical Microbiology , 1991 .

[16]  Donna R. Maglott,et al.  RefSeq and LocusLink: NCBI gene-centered resources , 2001, Nucleic Acids Res..

[17]  Nicholas M. Luscombe,et al.  Complete Genome Sequence of Uropathogenic Proteus mirabilis, a Master of both Adherence and Motility , 2008, Journal of bacteriology.

[18]  M. V. Bertacine Dias,et al.  Folate biosynthesis pathway: mechanisms and insights into drug design for infectious diseases. , 2018, Future medicinal chemistry.

[19]  R. Hage,et al.  Emerging Antibiotic Resistance to Bacterial Isolates from Human Urinary Tract Infections in Grenada , 2019, Cureus.

[20]  Carl Nathan,et al.  Antibiotic resistance--problems, progress, and prospects. , 2014, The New England journal of medicine.

[21]  M. Raeisi,et al.  Prevalence and antibiotic resistance pattern of bacteria isolated from urinary tract infections in Northern Iran , 2017, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[22]  J. Kerr,et al.  CORRECTION , 2003 .

[23]  Judith A. Blake,et al.  Gene Ontology annotations: what they mean and where they come from , 2008, BMC Bioinformatics.

[24]  G. Rossolini,et al.  Emerging Extended-Spectrum β-Lactamases in Proteus mirabilis , 2002, Journal of Clinical Microbiology.

[25]  S. S. Syed Sulaiman,et al.  Prescribing statins among patients with type 2 diabetes: The clinical gap between the guidelines and practice , 2019, Journal of Research in Medical Sciences.

[26]  Victor I Band,et al.  Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria , 2014, Antibiotics.

[27]  Trey Ideker,et al.  Cytoscape: the network visualization tool for GenomeSpace workflows , 2014, F1000Research.

[28]  P. Bradford,et al.  AcrAB Efflux Pump Plays a Role in Decreased Susceptibility to Tigecycline in Morganella morganii , 2005, Antimicrobial Agents and Chemotherapy.

[29]  P. Bork,et al.  Interactive Tree Of Life (iTOL) v4: recent updates and new developments , 2019, Nucleic Acids Res..

[30]  H. Mobley,et al.  Hemagglutinin, urease, and hemolysin production by Proteus mirabilis from clinical sources. , 1990, The Journal of infectious diseases.

[31]  Ibrahim H. Babikir,et al.  Uropathogens and their antimicrobial resistance patterns: Relationship with urinary tract infections , 2019, International journal of health sciences.

[32]  Feng Zhu,et al.  Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics , 2019, Nucleic Acids Res..

[33]  Mihai Pop,et al.  ARDB—Antibiotic Resistance Genes Database , 2008, Nucleic Acids Res..

[34]  Raymond Lo,et al.  CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database , 2016, Nucleic Acids Res..

[35]  Anand Anbarasu,et al.  Elucidating the multi-drug resistance mechanism of Enterococcus faecalis V583: A gene interaction network analysis. , 2020, Gene.

[36]  J. Mckinney,et al.  Targeting bacterial central metabolism for drug development. , 2014, Chemistry & biology.

[37]  Shui-Ping Wang.  Bacterial Two-Component Systems: Structures and Signaling Mechanisms , 2012 .

[38]  Brad T. Sherman,et al.  Extracting Biological Meaning from Large Gene Lists with DAVID , 2009, Current protocols in bioinformatics.

[39]  Anand Anbarasu,et al.  Role of SHV-11, a Class A β-Lactamase, Gene in Multidrug Resistance Among Klebsiella pneumoniae Strains and Understanding its Mechanism by Gene Network Analysis. , 2020, Microbial drug resistance.

[40]  Amr T. M. Saeb,et al.  Genome sequencing and analysis of the first spontaneous Nanosilver resistant bacterium Proteus mirabilis strain SCDR1 , 2016, Antimicrobial Resistance & Infection Control.

[41]  Anand Anbarasu,et al.  Evolutionary Relationship of Penicillin-Binding Protein 2 Coding penA Gene and Understanding the Role in Drug-Resistance Mechanism Using Gene Interaction Network Analysis , 2019, Lecture Notes on Multidisciplinary Industrial Engineering.

[42]  Anand Anbarasu,et al.  fabp4 is central to eight obesity associated genes: a functional gene network-based polymorphic study. , 2015, Journal of theoretical biology.

[43]  Gary D Bader,et al.  A travel guide to Cytoscape plugins , 2012, Nature Methods.

[44]  Sudha Ramaiah,et al.  Exploring the multi-drug resistance in Escherichia coli O157:H7 by gene interaction network: A systems biology approach. , 2019, Genomics.

[45]  H. Mobley,et al.  Pathogenesis of Proteus mirabilis Infection , 2018, EcoSal Plus.

[46]  P. Bradford,et al.  AcrAB Multidrug Efflux Pump Is Associated with Reduced Levels of Susceptibility to Tigecycline (GAR-936) in Proteus mirabilis , 2003, Antimicrobial Agents and Chemotherapy.

[47]  Andrew C. Pawlowski,et al.  The Comprehensive Antibiotic Resistance Database , 2013, Antimicrobial Agents and Chemotherapy.

[48]  P. Anitha,et al.  Computational gene network study on antibiotic resistance genes of Acinetobacter baumannii , 2014, Comput. Biol. Medicine.

[49]  Anand Anbarasu,et al.  Systems biology studies in Pseudomonas aeruginosa PA01 to understand their role in biofilm formation and multidrug efflux pumps. , 2019, Microbial pathogenesis.

[50]  Jessica N Schaffer,et al.  Proteus mirabilis and Urinary Tract Infections , 2015, Microbiology spectrum.

[51]  Anand Anbarasu,et al.  Gene interaction network studies to decipher the multi-drug resistance mechanism in Salmonella enterica serovar typhi CT18 reveal potential drug targets. , 2020, Microbial pathogenesis.

[52]  Brad T. Sherman,et al.  DAVID-WS: a stateful web service to facilitate gene/protein list analysis , 2012, Bioinform..

[53]  Anand Anbarasu,et al.  Gene and Protein Network Analysis of AmpC β Lactamase , 2015, Cell Biochemistry and Biophysics.

[54]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..

[55]  Sudha Ramaiah,et al.  Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools. , 2018, Gene.

[56]  Brian D. Ondov,et al.  Rapid Core-Genome Alignment and Visualization for Thousands of Intraspecific Microbial Genomes , 2014, bioRxiv.

[57]  Anand Anbarasu,et al.  Gene network analysis reveals the association of important functional partners involved in antibiotic resistance: A report on an important pathogenic bacterium Staphylococcus aureus. , 2016, Gene.

[58]  Yan Zhang,et al.  PATRIC, the bacterial bioinformatics database and analysis resource , 2013, Nucleic Acids Res..