Biosynthetic gene cluster signature profiles of pathogenic Gram-negative bacteria isolated from Egyptian clinical settings

• Published in: Microbiology spectrum 2023-10, Vol.11 (5), p.e0134423
• Main Authors: Abdelsalam, Nehal Adel, Elhadidy, Mohamed, Saif, Nehal A, Elsayed, Salma W, Mouftah, Shaimaa F, Sayed, Ahmed A, Ziko, Laila
• Format: Article
• Language: English
• Subjects: biosynthetic gene clusters; ESKAPE pathogens; natural products; specialized metabolites
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.01344-23

Biosynthetic gene clusters (BGCs) are a subset of consecutive genes present within a variety of organisms to produce specialized metabolites (SMs). These SMs are becoming a cornerstone to produce multiple medications including antibacterial and anticancer agents. Natural products (NPs) also play a pivotal role in enhancing the virulence of ESKAPE pathogens ( , , , , , and spp.), which represent a global health threat. We aimed to sequence and computationally analyze the BGCs present in 66 strains pertaining to three different ESKAPE pathogenic species: 21 , 28 , and 17 strains recovered from clinical settings in Egypt. DNA was extracted using QIAamp DNA Mini kit and Illumina NextSeq 550 was used for whole-genome sequencing. The sequences were quality-filtered by fastp and assembled by Unicycler. BGCs were detected by antiSMASH, BAGEL, GECCO, and PRISM, and aligned using Clinker. The highest abundance of BGCs was detected in (590), then (146) and the least in strains (133). isolates shared mostly the non-ribosomal peptide synthase (NRPS) type, isolates shared the ribosomally synthesized and post-translationally modified peptide-like (RiPP-like) type, while isolates shared the siderophore type. Most of the isolates harbored non-ribosomal peptide (NRP) BGCs with few isolates encoding polyketide BGCs. Sactipeptides and bottromycin BGCs were the most frequently detected RiPP clusters. We hypothesize that each species' BGC signature confers its virulence. Future experiments will link the detected clusters with their species and determine whether the encoded SMs are produced and cause their virulence. IMPORTANCE Our study analyzes the biosynthetic gene clusters (BGCs) present in 66 assemblies from clinical ESKAPE pathogen isolates pertaining to , , and strains. We report their sequencing and assembly followed by the analysis of their BGCs using several bioinformatics tools. We then focused on the most abundant BGC type in each species and we discussed their potential roles in the virulence of each species. This study is pivotal to further build on its experimental work that deciphers the role in virulence, possible antibacterial effects, and characterization of the encoded specialized metabolites (SMs). The study highlights the importance of studying the "harmful" BGCs and understanding the pathogenicity and virulence of those species, as well as possible benefits if the SMs were used as antibacterial agents. This could be the first study of its kind from Egypt a