CRISPR-Cas System: The Powerful Modulator of Accessory Genomes in Prokaryotes

Butiuc-Keul, Anca; Farkas, Anca; Carpa, Rahela; Iordache, Dumitrana

doi:10.1159/000516643

“…It should be noted, however, that most of AMR genes were identified in L. reuteri, which was also the species that showed less frequent CRISPR-Cas systems. This is in agreement with the idea that the consumption and dissemination of antibiotics in the environment is favouring the deficient forms of immunity provided by CRISPR-Cas systems [63].…”

Section: Discussionsupporting

confidence: 91%

Genomic diversity of genus Limosilactobacillus

Ksiezarek

¹

,

Grosso

²

,

Ribeiro

³

et al. 2022

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The genus Limosilactobacillus (formerly Lactobacillus ) contains multiple species considered to be adapted to vertebrates, yet their genomic diversity has not been explored. In this study, we performed comparative genomic analysis of Limosilactobacillus (22 species; 332 genomes) isolated from different niches, further focusing on human strains (11 species; 74 genomes) and their adaptation features to specific body sites. Phylogenomic analysis of Limosilactobacillus showed misidentification of some strains deposited in public databases and existence of putative novel Limosilactobacillus species. The pangenome analysis revealed a remarkable genomic diversity (only 1.3 % of gene clusters are shared), and we did not observe a strong association of the accessory genome with different niches. The pangenome of Limosilactobacillus reuteri and Limosilactobacillus fermentum was open, suggesting that acquisition of genes is still occurring. Although most Limosilactobacillus were predicted as antibiotic susceptible (83%), acquired antibiotic-resistance genes were common in L. reuteri from food-producing animals. Genes related to lactic acid isoform production (>95 %) and putative bacteriocins (70.2%) were identified in most Limosilactobacillus strains, while prophages (55.4%) and CRISPR-Cas systems (32.0%) were less prevalent. Among strains from human sources, several metabolic pathways were predicted as conserved and completed. Their accessory genome was highly variable and did not cluster according to different human body sites, with some exceptions (urogenital Limosilactobacillus vaginalis , Limosilactobacillus portuensis , Limosilactobacillus urinaemulieris and Limosilactobacillus coleohominis or gastrointestinal Limosilactobacillus mucosae ). Moreover, we identified 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues that were significantly enriched in strains from particular body sites. We concluded that evolution of the highly diverse Limosilactobacillus is complex and not always related to niche or human body site origin.

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“…Some of them may represent a life threat (e.g., phages) or a metabolic burden (e.g., plasmids) to which CRISPR–Cas systems represent a unique adaptative immunity defense mechanism. Studying the presence/absence of CRISPR–Cas systems and their features in different genera of families is a relatively new scientific approach to investigation to gain data on the evolution of these systems and their role played during the bacterial lifetime (Butiuc‐Keul et al, 2022). The average percentage of CRISPR distribution among Bacteria is the outcome of processes and/or factors that play different ecological roles within a genus/species.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic survey of CRISPR loci across 15 Serratia species

Scrascia

¹

,

Roberto

²

,

D’Addabbo

³

et al. 2023

MicrobiologyOpen

0

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The Clustered Regularly Interspaced Short Palindromic Repeats and CRISPRassociated proteins (CRISPR-Cas) system of prokaryotes is an adaptative immune defense mechanism to protect themselves from invading genetic elements (e.g., phages and plasmids). Studies that describe the genetic organization of these prokaryotic systems have mainly reported on the Enterobacteriaceae family (now reorganized within the order of Enterobacterales). For some genera, data on CRISPR-Cas systems remain poor, as in the case of Serratia (now part of the Yersiniaceae family) where data are limited to a few genomes of the species marcescens. This study describes the detection, in silico, of CRISPR loci in 146Serratia complete genomes and 336 high-quality assemblies available for the species

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“…The CRISPR/Cas system has the ability to degrade foreign incoming nucleic acids such as AMR gene encoding MGEs thereby acting as a bacterial immune system. CRISPR/Cas systems have shown potency to limit entry of plasmids into the bacterial cells and also cure them, which is explored to potentiate antibiotics (Butiuc-Keul et al, 2022). A study conducted by Tagliaferr et al, found a decreased expression of bla TEM-1 gene and decreased bla TEM-1 coding plasmid copy number in E. coli treated with CRISPR/Cas which thereby potentiated five β-lactam antibiotics (Tagliaferri et al, 2020).…”

Section: Crispr/cas Systemsmentioning

confidence: 99%

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

Narendrakumar

¹

,

Chakraborty

²

,

Kumari

³

et al. 2023

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β-lactam antibiotics are one of the most widely used and diverse classes of antimicrobial agents for treating both Gram-negative and Gram-positive bacterial infections. The β-lactam antibiotics, which include penicillins, cephalosporins, monobactams and carbapenems, exert their antibacterial activity by inhibiting the bacterial cell wall synthesis and have a global positive impact in treating serious bacterial infections. Today, β-lactam antibiotics are the most frequently prescribed antimicrobial across the globe. However, due to the widespread use and misapplication of β-lactam antibiotics in fields such as human medicine and animal agriculture, resistance to this superlative drug class has emerged in the majority of clinically important bacterial pathogens. This heightened antibiotic resistance prompted researchers to explore novel strategies to restore the activity of β-lactam antibiotics, which led to the discovery of β-lactamase inhibitors (BLIs) and other β-lactam potentiators. Although there are several successful β-lactam-β-lactamase inhibitor combinations in use, the emergence of novel resistance mechanisms and variants of β-lactamases have put the quest of new β-lactam potentiators beyond precedence. This review summarizes the success stories of β-lactamase inhibitors in use, prospective β-lactam potentiators in various phases of clinical trials and the different strategies used to identify novel β-lactam potentiators. Furthermore, this review discusses the various challenges in taking these β-lactam potentiators from bench to bedside and expounds other mechanisms that could be investigated to reduce the global antimicrobial resistance (AMR) burden.

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CRISPR-Cas System: The Powerful Modulator of Accessory Genomes in Prokaryotes

Cited by 16 publications

References 161 publications

Genomic diversity of genus Limosilactobacillus

Genomic diversity of genus Limosilactobacillus

Bioinformatic survey of CRISPR loci across 15 Serratia species

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

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