Comparison of CRISPR–Cas Immune Systems in Healthcare-Related Pathogens

Mortensen, Kate; Lam, Tony J.; Ye, Yuzhen

doi:10.3389/fmicb.2021.758782

Cited by 20 publications

(22 citation statements)

References 37 publications

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“…Some of the missing genes may be those involved in antibiotic resistance and originating from plasmids or integrative and conjugative elements, or those involved in virulence and originating from phages. This was mostly found in our study with ESKAPE pangenomes, and coincides with previous studies with the same species, except for the fact that we show a more complete collection of type IV systems, and we have used twice as many genomes (10,52).…”

Section: Discussionsupporting

confidence: 91%

“…There are different types of CRISPR-Cas systems based on genes that are part of the different steps of this immune system (adaptation or spacer integration, expression, and interference) and are generically called cas (CRISPR-associated genes). ESKAPE bacteria have CRISPR-Cas systems of the most common types, from I to IV, but only in a minimal number of strains, with frequencies ranging from less than 1% to 60% of genomes, depending on the species (10).…”

Section: Introductionmentioning

confidence: 99%

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Reducing CRISPR dark matter reveals a strong association between the bacterial membranome and CRISPR-Cas systems

Rubio

Sprang

Garzón

et al. 2022

Preprint

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Antimicrobial resistance is widely recognized as a serious global public health problem. To combat this threat, a thorough understanding of bacterial genomes is necessary. The current wide availability of bacterial genomes provides us with an in-depth understanding of the great variability of dispensable genes and their relationship with antimicrobials. Some of these accessory genes are those involved in CRISPR-Cas systems, which are acquired immunity systems that are present in part of bacterial genomes. They prevent viral infections through small DNA fragments called spacers. But the vast majority of these spacers have not yet been associated with the virus they recognize, and this has been named CRISPR dark matter (spacers without associated recognized sequence). By analyzing the spacers of tens of thousands of genomes from six bacterial species highly resistant to antibiotics, we have been able to reduce the CRISPR dark matter from 80-90% to 15% in some cases. In addition, we have observed that, when a genome presents CRISPR-Cas systems, this is accompanied by particular collections of membrane proteins. Our results suggest that when a bacterium presents membrane proteins that make it compete better in its environment, and these proteins are in turn receptors for specific phages, it would be forced to acquire CRISPR-Cas immunity systems to avoid infection by these phages.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Reducing CRISPR dark matter reveals a strong association between the bacterial membranome and CRISPR-Cas systems

Rubio

Sprang

Garzón

et al. 2022

Preprint

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“…Pseudomonas aeruginosa) and one genus (Enterobacter sp.) [30,31]. These pathogens are frequently involved in problematic nosocomial infections, due to their multi-drug resistance and/or invasive phenotypes [32][33][34][35][36][37].…”

Section: Bacterial Pathogens Belonging To the Eskape Panel Consist Of...mentioning

confidence: 99%

“…Bacterial pathogens belonging to the ESKAPE panel consist of five species ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa ) and one genus ( Enterobacter sp.) [30,31]. These pathogens are frequently involved in problematic nosocomial infections, due to their multi-drug resistance and/or invasive phenotypes [32–37].…”

Section: Introductionmentioning

confidence: 99%

The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

Botelho

Cazares

Schulenburg

2022

Preprint

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Mobile genetic elements (MGEs) mediate the shuffling of genes among organisms. They contribute to the spread of virulence and antibiotic resistance genes in human pathogens, including the particularly problematic group of ESKAPE pathogens, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. Here, we performed the first systematic analysis of MGEs, including plasmids, prophages, and integrative and conjugative/mobilizable elements (ICEs/IMEs), in the ESKAPE pathogens. We characterized over 1700 complete ESKAPE genomes and found that different MGE types are asymmetrically distributed across these pathogens. While some MGEs are capable of exchanging DNA beyond the genus (and phylum) barrier, horizontal gene transfer (HGT) is mainly restricted by phylum or genus. We further observed that most genes on MGEs have unknown functions and show intricate distribution patterns. Moreover, AMR genes and anti-CRISPRs are overrepresented in the ESKAPE mobilome. Our results also underscored species-specific trends shaping the number of MGEs, AMR, and virulence genes across pairs of conspecific ESKAPE genomes with and without CRISPR-Cas systems. Finally, we found that CRISPR targets vary according to MGE type: while plasmid CRISPRs almost exclusively target other plasmids, ICEs/IME CRISPRs preferentially target ICEs/IMEs and prophages. Overall, our study highlights the general importance of the ESKAPE mobilome in contributing to the spread of AMR and mediating conflict among MGEs.

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“…Although CRISPR-Cas systems are commonly found in prokaryotes, only about half of the bacterial species contain them [9,44]. We recently showed that human related bacterial species have a broad spectrum of the prevalence of the CRISPR-Cas systems; for example, Staphylococcus aureus has the least tendency of obtaining the CRISPR-Cas systems with only 0.55% of its isolates containing CRISPR-Cas systems, whereas most isolates of Clostridioides difficile analyzed have CRISPR-Cas systems each having multiple CRISPRs [54]. It is reflected in the Zhao2019 collection-isolates from 8 out of 12 individuals contain one or more of the CRISPR-Cas systems found in B. fragilis (see Table 2).…”

Section: Discussionmentioning

confidence: 99%

Diversity and dynamics of the CRISPR-Cas systems associated with Bacteroides fragilis in human population

Lam

Mortensen

2022

BMC Genomics

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Background CRISPR-Cas (clustered regularly interspaced short palindromic repeats—CRISPR-associated proteins) systems are adaptive immune systems commonly found in prokaryotes that provide sequence-specific defense against invading mobile genetic elements (MGEs). The memory of these immunological encounters are stored in CRISPR arrays, where spacer sequences record the identity and history of past invaders. Analyzing such CRISPR arrays provide insights into the dynamics of CRISPR-Cas systems and the adaptation of their host bacteria to rapidly changing environments such as the human gut. Results In this study, we utilized 601 publicly available Bacteroides fragilis genome isolates from 12 healthy individuals, 6 of which include longitudinal observations, and 222 available B. fragilis reference genomes to update the understanding of B. fragilis CRISPR-Cas dynamics and their differential activities. Analysis of longitudinal genomic data showed that some CRISPR array structures remained relatively stable over time whereas others involved radical spacer acquisition during some periods, and diverse CRISPR arrays (associated with multiple isolates) co-existed in the same individuals with some persisted over time. Furthermore, features of CRISPR adaptation, evolution, and microdynamics were highlighted through an analysis of host-MGE network, such as modules of multiple MGEs and hosts, reflecting complex interactions between B. fragilis and its invaders mediated through the CRISPR-Cas systems. Conclusions We made available of all annotated CRISPR-Cas systems and their target MGEs, and their interaction network as a web resource at https://omics.informatics.indiana.edu/CRISPRone/Bfragilis. We anticipate it will become an important resource for studying of B. fragilis, its CRISPR-Cas systems, and its interaction with mobile genetic elements providing insights into evolutionary dynamics that may shape the species virulence and lead to its pathogenicity.

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Comparison of CRISPR–Cas Immune Systems in Healthcare-Related Pathogens

Cited by 20 publications

References 37 publications

Reducing CRISPR dark matter reveals a strong association between the bacterial membranome and CRISPR-Cas systems

Reducing CRISPR dark matter reveals a strong association between the bacterial membranome and CRISPR-Cas systems

The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

Diversity and dynamics of the CRISPR-Cas systems associated with Bacteroides fragilis in human population

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