Jason Qian, Zhi-xiang Lu, Christopher P Mancuso, Han-Ying Jhuang, Roc{\'ıo del Carmen Barajas-Ornelas, Sarah A Boswell, Fernando H Ram{\'ırez-Guadiana, Victoria Jones, Akhila Sonti, Kole Sedlack, and others. 2020. “
Barcoded microbial system for high-resolution object provenance.” Science, 368, 6495, Pp. 1135–1140.
Lorena Preciado-Llanes, Anna Aulicino, Roc{\'ıo Canals, Patrick J Moynihan, Xiaojun Zhu, Ndaru Jambo, Tonney S Nyirenda, Innocent Kadwala, Ana Sousa Gerós, Siân V Owen, and others. 2020. “
Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease.” Proceedings of the National Academy of Sciences, 117, 34, Pp. 20717–20728.
Jared D Honeycutt, Nicolas Wenner, Yan Li, Susan M Brewer, Liliana M Massis, Sky W Brubaker, Phoom Chairatana, Sian V Owen, Rocio Canals, Jay CD Hinton, and others. 2020. “
Genetic variation in the MacAB-TolC efflux pump influences pathogenesis of invasive Salmonella isolates from Africa.” PLoS pathogens, 16, 8, Pp. e1008763.
Jared D. Honeycutt, Nicolas Wenner, Yan Li, Susan M. Brewer, Liliana M. Massis, Sky W. Brubaker, Phoom Chairatana, Siân V. Owen, Rocío Canals, Jay C. D. Hinton, and Denise M. Monack. 2020. “
Genetic variation in the MacAB-TolC efflux pump influences pathogenesis of invasive Salmonella isolates from Africa.” PLOS Pathogens, 16, 8, Pp. 1-30.
Publisher's VersionAbstractAuthor summary Salmonella Typhimurium will generally cause acute gut infections in humans. However, S. Typhimurium strains causing severe, systemic infections have emerged in sub-Saharan Africa and are phylogenetically distinct from other S. Typhimurium strains. Our comparative genomic analysis revealed S. Typhimurium sequence-type 313 (ST313) from Africa have notable sequence variations within the macA and macB genes. These genes are already known to play a role in Salmonella pathogenesis and are otherwise conserved in Salmonella and many other Gram-negative bacteria. We show that regulation of macAB transcription depends, in part, on the key Salmonella virulence system PhoP/Q and that expression of MacAB improves Salmonella resistance to an antimicrobial peptide. African macAB variants interfere with this antimicrobial peptide resistance function and can alter Salmonella replication within macrophages. Using competitive infection experiments in mice, we see that these macAB variants influence fitness in the mammalian gut and systemic sites, with African S. Typhimurium reliant upon its macAB genotype for systemic infection of susceptible hosts. These results suggest that the evolution of African S. Typhimurium has been shaped by human populations with impaired ability to control intracellular Salmonella infections.
Jason Qian, Zhi-xiang Lu, Christopher P. Mancuso, Han-Ying Jhuang, Rocío del Carmen Barajas-Ornelas, Sarah A. Boswell, Fernando H. Ramírez-Guadiana, Victoria Jones, Akhila Sonti, Kole Sedlack, Lior Artzi, Giyoung Jung, Mohammad Arammash, Mary E. Pettit, Michael Melfi, Lorena Lyon, Siân V. Owen, Michael Baym, Ahmad S. Khalil, Pamela A. Silver, David Z. Rudner, and Michael Springer. 2020. “
Barcoded microbial system for high-resolution object provenance.” Science, 368, 6495, Pp. 1135–1140.
Publisher's VersionAbstractUnder adverse environmental conditions, some microorganisms form spores that provide robust protection for genetic material. Qian et al. developed a system in which DNA barcodes are encapsulated inside nongerminating microbial spores and can be dispersed on objects or in the environment (see the Perspective by Nivala). These barcoded spores provide a durable, specific marker that can be read out quickly with simple equipment. When applied to soil, the spores can be transferred to and from objects around them, enabling tracking at meter-scale resolution. On plant leaves, the spores are not readily transferred, and the authors demonstrate a potential use for tracking agricultural products.Science, this issue p. 1135; see also p. 1058Determining where an object has been is a fundamental challenge for human health, commerce, and food safety. Location-specific microbes in principle offer a cheap and sensitive way to determine object provenance. We created a synthetic, scalable microbial spore system that identifies object provenance in under 1 hour at meter-scale resolution and near single-spore sensitivity and can be safely introduced into and recovered from the environment. This system solves the key challenges in object provenance: persistence in the environment, scalability, rapid and facile decoding, and biocontainment. Our system is compatible with SHERLOCK, a Cas13a RNA-guided nucleic acid detection assay, facilitating its implementation in a wide range of applications.
Lorena Preciado-Llanes, Anna Aulicino, Rocío Canals, Patrick J. Moynihan, Xiaojun Zhu, Ndaru Jambo, Tonney S. Nyirenda, Innocent Kadwala, Ana Sousa Gerós, Siân V. Owen, Kondwani C. Jambo, Benjamin Kumwenda, Natacha Veerapen, Gurdyal S. Besra, Melita A. Gordon, Jay C. D. Hinton, Giorgio Napolitani, Mariolina Salio, and Alison Simmons. 2020. “
Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease.” Proceedings of the National Academy of Sciences.
Publisher's VersionAbstractNontyphoidal Salmonella serotypes are a common cause of self-limiting diarrhoeal illnesses in healthy adults. However, recently, a highly invasive multidrug resistant Salmonella Typhimurium sequence type 313 has emerged as a major cause of morbidity and mortality in sub-Saharan Africa, particularly in children and immunosuppressed individuals. In this paper we describe escape from MAIT cell recognition as an additional mechanism of immune evasion of S. Typhimurium ST313. As MAIT cells represent an early defense mechanism against pathogens at mucosal surfaces, and their frequency and function are altered in immunosuppressed individuals in sub-Saharan Africa, harnessing their function may offer an important therapeutic strategy to improve mucosal immunity.Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified. We report that typhoidal and nontyphoidal Salmonella enterica strains activate MAIT cells. However, S. Typhimurium sequence type 313 (ST313) lineage 2 strains, which are responsible for the burden of multidrug-resistant nontyphoidal invasive disease in Africa, escape MAIT cell recognition through overexpression of ribB. This bacterial gene encodes the 4-dihydroxy-2-butanone-4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. The MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of S. Typhimurium ST313 lineage 2.All data have been made available in the manuscript.
Siân V. Owen*, Rocío Canals, Nicolas Wenner, Disa L. Hammarlöf, Carsten Kröger, and Jay C. D. Hinton. 2020. “
A window into lysogeny: revealing temperate phage biology with transcriptomics.” Microbial Genomics.
Publisher's VersionAbstractProphages are integrated phage elements that are a pervasive feature of bacterial genomes. The fitness of bacteria is enhanced by prophages that confer beneficial functions such as virulence, stress tolerance or phage resistance, and these functions are encoded by ‘accessory’ or ‘moron’ loci. Whilst the majority of phage-encoded genes are repressed during lysogeny, accessory loci are often highly expressed. However, it is challenging to identify novel prophage accessory loci from DNA sequence data alone. Here, we use bacterial RNA-seq data to examine the transcriptional landscapes of five
Salmonella prophages. We show that transcriptomic data can be used to heuristically enrich for prophage features that are highly expressed within bacterial cells and represent functionally important accessory loci. Using this approach, we identify a novel antisense RNA species in prophage BTP1, STnc6030, which mediates superinfection exclusion of phage BTP1. Bacterial transcriptomic datasets are a powerful tool to explore the molecular biology of temperate phages.