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Metagenomic Survey of Hospital Sites Uncovers Two Ecological Niches Contributing to Infections

NEW YORK – There are two broad microbial communities within hospitals that may contribute to hospital-acquired infections, according to a new metagenomic sequencing study.

Hospital-acquired infections are a continuing issue in healthcare, as there are about 721,800 such infections each year in the US. These infections are further exacerbated by antibiotic resistance and the emergence of multidrug-resistant organisms.

A Genome Institute of Singapore-led team of researchers conducted a metagenomic survey of different sites in a hospital over time. Their metagenomic sequencing-based analysis revealed two ecological niches, one influenced by the ability to form biofilms and the other by the human microbiome, as they reported Monday in Nature Medicine. Both community types housed antibiotic resistance genes, and a combination of culturing and nanopore sequencing further examined the diversity of resistance and other genes among these microbes.

"These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections," senior author Niranjan Nagarajan from the Genome Institute of Singapore and his colleague wrote in their paper.

The researchers sampled 179 sites within a tertiary hospital in Singapore, including sink traps, pulse oximeters, and door handles, among others. They collected the first round of samples in November 2017 and the second round a few days later. A third round of samples were collected from 80 of the sites about a year and a half later, in May 2019.

Following Illumina shotgun metagenomic sequencing, the researchers conducted a principal coordinates analysis of the taxonomic profiles they generated to reveal two distinct microbial communities from within the hospital. Overall, community type A sites were more taxonomically diverse and were associated with surfaces that are touched frequently by patients and healthcare workers. Community type B sites, meanwhile, were sites like sink traps that have increasingly been of concern to hospital infection control teams because of their likelihood to house multidrug-resistant organisms. 

While microbiomes associated with the two community types exhibited varying degrees of stability, the researchers noted that community type B sites like sink traps and aerators tended to be more stable with less microbial turnover and influence by biofilm formation, and community type A sites exhibited a greater influence from the human microbiome.

The two community types also harbored different antibiotic resistance genes. In general, community type A sites had a wider array of resistance genes that were present at lower levels, including oxa-23 and mecA, which confer resistance to carbapenem and methicillin, respectively. Community type B sites, meanwhile, more commonly harbored microbes with the imp-1 and cme-1 resistance genes.

The researchers also cultured staples they collected, and following antibiotic selection sequenced them using Oxford Nanopore's GridIon system to generate long-read metagenomic sequences, including phage and plasmid sequences. 

By analyzing the evolutionary relationships between the microbes sampled at different timepoints, the researchers noted a number of the microbial genomes samples in May 2019 clustered with samples from the earlier time points and differed by only a few SNPs, suggesting a continuity of infection.

The researchers also uncovered novel combinations of antibiotic resistance genes among these genomes and plasmids. One novel combination that they in particular highlighted as worrisome was plasmids containing both antibiotic and disinfectant resistance genes. This combination, they added, suggests hospital cleaning approaches could be selecting for more antibiotic-resistant organisms.

According to the researchers, their findings indicate that surveys like theirs, combined with periodic follow-up surveys, could help guide hospital infection control and cleaning efforts. "With further improvements in the cost and ease of short-read sequencing, hospital-wide surveys will be increasingly feasible, provide valuable information for infection control, and eventually be part of routine practice," they wrote.