# Molecular epidemiology and population structure of Providencia stuartii obtained from humans and other sources

## TL;DR

This study analyzes the genetic diversity and global spread of the antibiotic-resistant bacterium Providencia stuartii using a new MLST method and identifies high-risk clones.

## Contribution

A novel non-PCR-based MLST scheme for P. stuartii and a public web platform for species classification and sequence typing.

## Key findings

- 104 distinct sequence types were identified, revealing high genetic diversity in P. stuartii.
- Multidrug-resistant global clones like ST72 and ST12 were found in both human and non-human sources.
- ST19 and ST90 in Mexico are linked to NDM-1 and IncA/C2 plasmid replicon.

## Abstract

Providencia stuartii is an emerging opportunistic pathogen in humans and belongs to a genus that has shown great genomic diversity. P. stuartii has shown relevant traits in antimicrobial resistance because of its intrinsic resistance to multiple antibiotics and its ability to acquire resistance genes that limit therapeutic options. The present study describes the molecular epidemiology of P. stuartii based on the multilocus sequence typing (MLST) scheme developed for this purpose. This non-PCR-based scheme uses seven complete housekeeping genes. In total, 518 genomes obtained from public databases and Mexican isolates were evaluated. These genomes were from different sources, such as human infections, followed by insects, wastewater, animals, and unknown origins. The molecular epidemiology showed 104 distinct sequence types (STs). We identified global clones that are multidrug-resistant and are widely geographically distributed; for instance, the ST72 (belonging to main clonal complex [CC1]), the major sequence type in P. stuartii, ST12 was present in human and non-human niches, and the ST19 and ST90 (present in Mexico) are associated with NDM-1 and the IncA/C2 plasmid replicon. This study provides a tool for a more accurate analysis of the molecular epidemiology of P. stuartii obtained from different sources and revises its genetic diversity and global distribution. In addition, this work developed a public web platform (http://mlstps.insp.mx) that implements average nucleotide identity tool for correct species classification followed by the ST assignation. This MLST scheme might be useful for future studies that focus on the evolution of this pathogen and monitoring the global problem clones.

Providencia stuartii is of particular concern due to its natural resistance to antibiotics, such as colistin and tigecycline, as well as its increasing resistance to carbapenems. Consequently, P. stuartii is an emerging pathogen that has been reported as a cause of human infections and is also distributed in non-human niches such as insects, wastewater, and animals. To understand how bacteria spread, researchers study their “genetic fingerprint” using methods like multilocus sequence typing (MLST), which for decades has been a useful approach for studying the molecular epidemiology of pathogens. Therefore, in this study, we studied the genetic diversity of P. stuartii implementing an MLST scheme designed for this purpose. We identified multidrug-resistant clones that are distributed worldwide. This system could be useful for future studies focusing on the evolution of this pathogen and monitoring high-risk clones. Tracking these strains is important for protecting public health and preventing outbreaks.