Abstract
The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridium difficile have been identified as the leading global cause of multidrug-resistant bacterial infections in hospitals. CRISPR–Cas systems are bacterial immune systems, empowering the bacteria with defense against invasive mobile genetic elements that may carry the antimicrobial resistance (AMR) genes, among others. On the other hand, the CRISPR–Cas systems are themselves mobile. In this study, we annotated and compared the CRISPR–Cas systems in these pathogens, utilizing their publicly available large numbers of sequenced genomes (e.g., there are more than 12 thousands of S. aureus genomes). The presence of CRISPR–Cas systems showed a very broad spectrum in these pathogens: S. aureus has the least tendency of obtaining the CRISPR–Cas systems with only 0.55% of its isolates containing CRISPR–Cas systems, whereas isolates of C. difficile we analyzed have CRISPR–Cas systems each having multiple CRISPRs. Statistical tests show that CRISPR–Cas containing isolates tend to have more AMRs for four of the pathogens (A. baumannii, E. faecium, P. aeruginosa, and S. aureus). We made available all the annotated CRISPR–Cas systems in these pathogens with visualization at a website (https://omics.informatics.indiana.edu/CRISPRone/pathogen), which we believe will be an important resource for studying the pathogens and their arms-race with invaders mediated through the CRISPR–Cas systems, and for developing potential clinical applications of the CRISPR–Cas systems for battles against the antibiotic resistant pathogens.
Highlights
ESKAPE pathogens are the primary cause of nosocomial infections and are of global concern due to the increasing emergence of multi-drug resistant (MDR) bacteria (Zohra et al, 2021)
In P. aeruginosa only Type-I clustered regularly inter-spaced short palindromic repeats (CRISPRs)– Cas systems were found in this species with a prevalence of 60.33% (Figure 2C)
We note that K. pneumoniae was found to have a greater number of antimicrobial resistance (AMR) genes in CRISPR containing isolates compared to isolates without CRISPR–Cas system
Summary
ESKAPE pathogens are the primary cause of nosocomial infections (infections contracted from a healthcare setting) and are of global concern due to the increasing emergence of multi-drug resistant (MDR) bacteria (Zohra et al, 2021). CRISPR–Cas Systems in Healthcare-Related Pathogens effectively “escape” the limited bank of available antibiotics by acquiring antimicrobial resistance (AMR) genes. Based on the specific combination of cas genes, CRISPR–Cas immune systems can be divided into two classes (I and II), each containing several types and subtypes (Makarova et al, 2020) These systems have recently been engineered to achieve guided genome editing and gene expression regulation in many different organisms, including mammalian cells (Hendriks et al, 2020). We systematically analyze the large number of publicly available ESKAPE genomes, focusing on the CRISPR–Cas immune systems and AMR genes and their relationship, and present our findings as an important resource to study ESKAPE pathogens, their potential invaders, and to develop potential clinical alternatives to against antibiotic resistant pathogens
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