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Gatesy, S. W.

Publications and source records attributed to Gatesy, S. W..

3 recordsLinked to original sources

Genomic evaluation of a case of Lacticaseibacillus rhamnosus endocarditis: comparison with commercial yogurt isolates and examination of global population structure

Probiotics, including yogurt commonly containing bacteria of the Lactobacillus group, are widely used to promote microbiome health and to prevent gastrointestinal or other infections, especially in the setting of antibiotic use. Rarely, however, Lactobacillus bacteria have caused invasive or severe infections in patients. In this report, we present a patient with fatal Lacticaseibacillus bacteremia and endocarditis who frequently consumed yogurt. Whole genome sequencing identified the patients bloodstream isolate as Lacticaseibacillus (formerly Lactobacillus) rhamnosus, and sequencing of Lactobacillus isolates from selected commercial yogurt preparations revealed one isolate nearly identical to the patients isolate, differing by only one nucleotide (adenine to guanine substitution leading to a M1A amino acid change in the start codon of the nrdR gene). To place these sequences into broader context of L. rhamnosus strains, we compared them to 602 L. rhamnosus genome sequences publicly available through the National Center for Biotechnology Information repository. Both isolates belonged to a clade, identified in this report as clade YC, composed of mostly gastrointestinal isolates from healthy individuals, some of which also differed by only a single nucleotide from the patients isolate. Members of clade YC had only rarely been previously identified in invasive infections. In summary, the Lacticaseibacillus strain causing this patients infection may have originated from a commercial dairy product or from the commensal flora of his gastrointestinal tract. This study demonstrates that whole genome sequencing may be insufficient to reliably determine the source of invasive infections caused by L. rhamnosus. IMPORTANCEActive culture and probiotic foods and supplements are often used to promote gut health. Though largely considered safe for human consumption, there are rare reports of severe infections linked to bacterial species used in these products. Using whole genome sequencing, we examined a case of fatal infection with Lacticaseibacillus rhamnosus in the patients blood. By comparing the bacterial genome sequence from the patient to strains cultured from 4 commercial yogurt samples and 602 publicly available sequences of L. rhamnosus from around the world, we found that it was nearly identical to one of the yogurt strains and equally similar to other strains from both probiotics and healthy individuals gastrointestinal tracts. These findings show that even with whole genome sequencing it can be difficult to determine the source of an invasive L. rhamnosus infection, whether from recent consumption of a probiotic or dairy product versus from the gastrointestinal microbiome.

microbiology↗

Genomic and phenotypic characterization of Pseudomonas hygromyciniae, a novel bacterial species discovered from a commercially purchased antibiotic

A purchased lot of the antibiotic hygromycin B was found to be contaminated with a novel bacterial species, which we designate Pseudomonas hygromyciniae. Characteristics of P. hygromyciniae include its ability to use a variety of compounds as carbon sources, its pathogenicity towards lettuce and Galleria mellonella, and its ability to inhibit the growth of an E. coli strain. P. hygromyciniae is unlikely to be a human pathogen, as it did not survive at 37 {degrees}C and was not cytotoxic towards a mammalian cell line. The P. hygromyciniae strain harbors a novel 250 kb megaplasmid which confers resistance to hygromycin B and contains numerous other genes predicted to encode replication and conjugation machinery. These findings indicate that commercially manufactured antibiotics represent another extreme environment that may support the growth of novel bacterial species. IMPORTANCEMicrobial ecologists have surveyed numerous natural and manmade environments in search of new microbial species. In some instances, these microbes are discovered in harsh conditions, such as deep-sea vents, and their discovery leads to better understanding of how microbes adapt to their environment. Here, we have discovered a new species of bacteria from an extreme manmade environment: a lyophilized, commercially available bottle of the antibiotic hygromycin B.

microbiology↗

Functional and Structural Characterization of OXA-935, a Novel OXA-10-family β-lactamase from Pseudomonas aeruginosa

Resistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic {beta}-lactamase AmpC. However, OXA-10-family {beta}-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA {beta}-lactamases have a propensity for mutation leading to extended spectrum cephalosporinase and carbapenemase activity. In this study, we identified isolates from a subclade of the multidrug-resistant (MDR) high risk clonal complex CC446 with resistance to ceftazidime. Genomic analysis revealed that these isolates harbored a plasmid containing a novel allele of blaOXA-10, named blaOXA-935, which was predicted to produce an OXA-10 variant with two amino acid substitutions: an aspartic acid instead of glycine at position 157 and a serine instead of phenylalanine at position 153. The G157D mutation, present in OXA-14, is associated with resistance to ceftazidime. Deletion of blaOXA-935 restored sensitivity to ceftazidime and susceptibility profiling of P. aeruginosa laboratory strains expressing blaOXA-935 revealed that OXA-935 conferred ceftazidime resistance. To better understand the impact of the variant amino acids, we determined the crystal structures of OXA-14 and OXA-935. In OXA-14, one of two monomers contained the canonical carbamylated lysine-70 (K70). In contrast, both monomers of OXA-935 were decarbamylated at K70, and the F153S mutation conferred increased flexibility to the omega ({Omega}) loop. Compared to OXA-14, the catalytic efficiency of OXA-935 for nitrocefin was significantly reduced. Amino acid changes that confer extended spectrum cephalosporinase activity to OXA-10-family {beta}-lactamases are concerning given rising reliance on novel {beta}-lactam/{beta}-lactamase inhibitor combinations such as ceftolozane-tazobactam and ceftazidime-avibactam to treat MDR P. aeruginosa infections.

microbiology↗