Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection

Antón Ambroa; Lucia Blasco; María López; Olga Pacios; Inés Bleriot; Laura Fernández-García; Manuel González de Aledo; Concha Ortiz-Cartagena; Andrew Millard; María Tomás

doi:10.3389/fmicb.2021.784949

Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection

Front Microbiol. 2022 Feb 17:12:784949. doi: 10.3389/fmicb.2021.784949. eCollection 2021.

Authors

Antón Ambroa^{1

2}, Lucia Blasco^{1

2}, María López^{1

2

3}, Olga Pacios^{1

2}, Inés Bleriot^{1

2}, Laura Fernández-García^{1

2}, Manuel González de Aledo¹, Concha Ortiz-Cartagena^{1

2}, Andrew Millard⁴, María Tomás^{1

2

3}

Affiliations

¹ Microbiology Department-Research Institute Biomedical A Coruña (INIBIC), Hospital A Coruña (CHUAC), University of A Coruña (UDC), A Coruña, Spain.
² Study Group on Mechanisms of Action and Resistance to Antimicrobials (GEMARA) the Behalf of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain.
³ Spanish Network for Research in Infectious Diseases (REIPI), Infectious Diseases Network Biomedical Research Center (CIBERINFEC), Carlos III Health Institute, Madrid, Spain.
⁴ Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.

Abstract

To optimize phage therapy, we need to understand how bacteria evolve against phage attacks. One of the main problems of phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage-resistant strains that can be overcome by the analysis of metadata provided by whole-genome sequencing. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strains belonging to the ST-2 clonal complex during a decade (Ab2000 vs. 2010): 9 from 2000 to 9 from 2010. The presence of genes putatively associated with phage resistance was detected. Genes detected were associated with an abortive infection system, restriction-modification system, genes predicted to be associated with defense systems but with unknown function, and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands in the 2000 strains and 32% in the 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems. A moderately higher presence of these genes in the strains of 2010 in comparison with those of 2000 was found, especially those related to the restriction-modification system and CRISPR-Cas system. The presence of these genes in genomic islands at a higher rate in the strains of 2010 compared with those of 2000 was also detected. Whole-genome sequencing and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in possible phage therapy.

Keywords: Acinetobacter baumannii; CRISPR; WGS or whole-genome sequencing; bacterial; genomic island; phages; resistance.