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Biology subjects

Saavedra, M. O.

Publications and source records attributed to Saavedra, M. O..

3 recordsLinked to original sources

Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas

We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. These genomes were from the viruses causing infections in the earliest recognized phase of the pandemic affecting Houston. Substantial viral genomic diversity was identified, which we interpret to mean that the virus was introduced into Houston many times independently by individuals who had traveled from different parts of the country and the world. The majority of viruses are apparent progeny of strains derived from Europe and Asia. We found no significant evidence of more virulent viral types, stressing the linkage between severe disease, underlying medical conditions, and perhaps host genetics. We discovered a signal of selection acting on the spike protein, the primary target of massive vaccine efforts worldwide. The data provide a critical resource for assessing virus evolution, the origin of new outbreaks, and the effect of host immune response. SignificanceCOVID-19, the disease caused by the SARS-CoV-2 virus, is a global pandemic. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. We identified no evidence that a particular strain or its progeny causes more severe disease, underscoring the connection between severe disease, underlying health conditions, and host genetics. Some amino acid replacements in the spike protein suggest positive immune selection is at work in shaping variation in this protein. Our analysis traces the early molecular architecture of SARS-CoV-2 in Houston, and will help us to understand the origin and trajectory of future infection spikes.

genetics↗

Genetic heterogeneity of the Spy1336/R28 - Spy1337 Virulence Axis in Streptococcus pyogenes and Effect on Gene Transcript Levels and Pathogenesis

Streptococcus pyogenes is a strict human pathogen responsible for more than 700 million infections annually worldwide. Strains of serotype M28 S. pyogenes are typically among the five more abundant types causing invasive infections and pharyngitis in adults and children. Type M28 strains also have an unusual propensity to cause puerperal sepsis and neonatal disease. We recently discovered that a one-nucleotide indel in an intergenic homopolymeric tract located between genes Spy1336/R28 and Spy1337 altered virulence in a mouse model of infection. In the present study, we analyzed size variation in this homopolymeric tract and determined the extent of heterogeneity in the number of tandemly-repeated 79-amino acid domains in the coding region of Spy1336/R28 in large samples of strains recovered from humans with invasive infections. Both repeat sequence elements are highly polymorphic in natural populations of M28 strains. Variation in the homopolymeric tract results in (i) changes in transcript levels of Spy1336/R28 and Spy1337 in vitro, (ii) differences in virulence in a mouse model of necrotizing myositis, and (iii) global transcriptome changes as shown by RNAseq analysis of isogenic mutant strains. Variation in the number of tandem repeats in the coding sequence of Spy1336/R28 is responsible for size variation of R28 protein in natural populations. Isogenic mutant strains in which genes encoding R28 or transcriptional regulator Spy1337 are inactivated are significantly less virulent in a nonhuman primate model of necrotizing myositis. Our findings provide impetus for additional studies addressing the role of R28 and Spy1337 variation in pathogen-host interactions.

microbiology↗

Discovery and whole genome sequencing of a human clinical isolate of the novel species Klebsiella quasivariicola sp. nov.

Originally thought to be a single species, Klebsiella pneumoniae has been divided into three distinct species: K. pneumoniae, K. quasipneumoniae and K. variicola. In a recent study of 1,777 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella strains recovered from human infections in Houston, we discovered one strain (KPN1705) causing a wound infection that was phylogenetically distinct from all currently recognized Klebsiella species. Whole genome sequencing of strain KPN1705 revealed that it was single locus variant of the multilocus sequence type ST-1155. This sequence type was reported only once previously. To further investigate the phylogeny of these two organisms, we sequenced the genome of strain KPN1705 to closure and compared its genetic features to Klebsiella reference strains. Results demonstrated strain KPN1705 extensively shares core gene content, antimicrobial resistance genes, and plasmids with K. pneumoniae, K. quasipneumoniae and K. variicola. Since strain KPN1705 and the previously reported novel strain are phylogenetically most closely related to K. variicola, we propose the name K. quasivariicola sp. nov.

microbiology↗