Rapid Microevolution of Biofilm Cells in Response to Antibiotics

Overview

Journal NPJ Biofilms Microbiomes

Date 2019 Nov 16

PMID 31728201

Citations 52

Authors

Anahit Penesyan

Stephanie S Nagy

Staffan Kjelleberg

Michael R Gillings

Ian T Paulsen

Affiliations

Soon will be listed here.

Abstract

Infections caused by are increasingly antibiotic resistant, generating a significant public health problem. Like many bacteria, adopts a biofilm lifestyle that enhances its antibiotic resistance and environmental resilience. Biofilms represent the predominant mode of microbial life, but research into antibiotic resistance has mainly focused on planktonic cells. We investigated the dynamics of biofilms in the presence of antibiotics. A 3-day exposure of biofilms to sub-inhibitory concentrations of antibiotics had a profound effect, increasing biofilm formation and antibiotic resistance in the majority of biofilm dispersal isolates. Cells dispersing from biofilms were genome sequenced to identify mutations accumulating in their genomes, and network analysis linked these mutations to their phenotypes. Transcriptomics of biofilms confirmed the network analysis results, revealing novel gene functions of relevance to both resistance and biofilm formation. This approach is a rapid and objective tool for investigating resistance dynamics of biofilms.

Citing Articles

Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts.

Almatroudi A Biology (Basel). 2025; 14(2).

PMID: 40001933 PMC: 11852148. DOI: 10.3390/biology14020165.

Phenotypic and genetic heterogeneity of in the course of an animal chronic infection.

Bednarczuk L, Chassard A, Plantade J, Charpentier X, Laaberki M Microb Genom. 2025; 11(2).

PMID: 39969275 PMC: 11840173. DOI: 10.1099/mgen.0.001352.

Novel Leech Antimicrobial Peptides, Hirunipins: Real-Time 3D Monitoring of Antimicrobial and Antibiofilm Mechanisms Using Optical Diffraction Tomography.

Kumar S, Park J, Radhakrishnan N, Aryal Y, Jeong G, Pyo I Adv Sci (Weinh). 2025; 12(10):e2409803.

PMID: 39792785 PMC: 11905058. DOI: 10.1002/advs.202409803.

Comprehensive Approaches to Combatting Biofilms: From Biofilm Structure to Phage-Based Therapies.

Grygiel I, Bajrak O, Wojcicki M, Krusiec K, Jonczyk-Matysiak E, Gorski A Antibiotics (Basel). 2024; 13(11).

PMID: 39596757 PMC: 11591314. DOI: 10.3390/antibiotics13111064.

Combating biofilm-associated Klebsiella pneumoniae infections using a bovine microbial enzyme.

Ramakrishnan R, Nair A, Parmar K, Rajmani R, Chakravortty D, Das D NPJ Biofilms Microbiomes. 2024; 10(1):119.

PMID: 39500915 PMC: 11538315. DOI: 10.1038/s41522-024-00593-7.

References

Castro J, Franca A, Bradwell K, Serrano M, Jefferson K, Cerca N . Comparative transcriptomic analysis of biofilms vs. planktonic cultures using RNA-seq. NPJ Biofilms Microbiomes. 2017; 3:3. PMC: 5460279. DOI: 10.1038/s41522-017-0012-7. View

Costerton J, Lewandowski Z, Caldwell D, Korber D, Lappin-Scott H . Microbial biofilms. Annu Rev Microbiol. 1995; 49:711-45. DOI: 10.1146/annurev.mi.49.100195.003431. View

Drlica K, Zhao X . DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997; 61(3):377-92. PMC: 232616. DOI: 10.1128/mmbr.61.3.377-392.1997. View

Lopez E, Blazquez J . Effect of subinhibitory concentrations of antibiotics on intrachromosomal homologous recombination in Escherichia coli. Antimicrob Agents Chemother. 2009; 53(8):3411-5. PMC: 2715609. DOI: 10.1128/AAC.00358-09. View

Venkatesh R, Ganesh N, Guhan N, Reddy M, Chandrasekhar T, Muniyappa K . RecX protein abrogates ATP hydrolysis and strand exchange promoted by RecA: insights into negative regulation of homologous recombination. Proc Natl Acad Sci U S A. 2002; 99(19):12091-6. PMC: 129403. DOI: 10.1073/pnas.192178999. View

Eijkelkamp B, Stroeher U, Hassan K, Elbourne L, Paulsen I, Brown M . H-NS plays a role in expression of Acinetobacter baumannii virulence features. Infect Immun. 2013; 81(7):2574-83. PMC: 3697591. DOI: 10.1128/IAI.00065-13. View

Shigeta M, Tanaka G, Komatsuzawa H, Sugai M, Suginaka H, Usui T . Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: a simple method. Chemotherapy. 1997; 43(5):340-5. DOI: 10.1159/000239587. View

Robinson C, Matos C, Beck D, Ren C, Lawrence J, Vasisht N . Transport and proofreading of proteins by the twin-arginine translocation (Tat) system in bacteria. Biochim Biophys Acta. 2010; 1808(3):876-84. DOI: 10.1016/j.bbamem.2010.11.023. View

Linares J, Gustafsson I, Baquero F, Martinez J . Antibiotics as intermicrobial signaling agents instead of weapons. Proc Natl Acad Sci U S A. 2006; 103(51):19484-9. PMC: 1682013. DOI: 10.1073/pnas.0608949103. View

10.

Peleg A, Adams J, Paterson D . Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2007; 51(6):2065-9. PMC: 1891386. DOI: 10.1128/AAC.01198-06. View

11.

Tomaras A, Dorsey C, Edelmann R, Actis L . Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology (Reading). 2003; 149(Pt 12):3473-3484. DOI: 10.1099/mic.0.26541-0. View

12.

OToole G, Kolter R . Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis. Mol Microbiol. 1998; 28(3):449-61. DOI: 10.1046/j.1365-2958.1998.00797.x. View

13.

Beaber J, Hochhut B, Waldor M . SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature. 2003; 427(6969):72-4. DOI: 10.1038/nature02241. View

14.

Finn R, Attwood T, Babbitt P, Bateman A, Bork P, Bridge A . InterPro in 2017-beyond protein family and domain annotations. Nucleic Acids Res. 2016; 45(D1):D190-D199. PMC: 5210578. DOI: 10.1093/nar/gkw1107. View

15.

Gallagher L, Ramage E, Weiss E, Radey M, Hayden H, Held K . Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter baumannii. J Bacteriol. 2015; 197(12):2027-35. PMC: 4438207. DOI: 10.1128/JB.00131-15. View

16.

Berne C, Ducret A, Hardy G, Brun Y . Adhesins Involved in Attachment to Abiotic Surfaces by Gram-Negative Bacteria. Microbiol Spectr. 2015; 3(4). PMC: 4566860. DOI: 10.1128/microbiolspec.MB-0018-2015. View

17.

Zhu Y, Zhao Y, Li B, Huang C, Zhang S, Yu S . Continental-scale pollution of estuaries with antibiotic resistance genes. Nat Microbiol. 2017; 2:16270. DOI: 10.1038/nmicrobiol.2016.270. View

18.

Peleg A, de Breij A, Adams M, Cerqueira G, Mocali S, Galardini M . The success of acinetobacter species; genetic, metabolic and virulence attributes. PLoS One. 2012; 7(10):e46984. PMC: 3483291. DOI: 10.1371/journal.pone.0046984. View

19.

Hoyle B, Costerton J . Bacterial resistance to antibiotics: the role of biofilms. Prog Drug Res. 1991; 37:91-105. DOI: 10.1007/978-3-0348-7139-6_2. View

20.

Tamayo R, Pratt J, Camilli A . Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu Rev Microbiol. 2007; 61:131-48. PMC: 2776827. DOI: 10.1146/annurev.micro.61.080706.093426. View