Biology subjects

Shapiro, B. J.

Publications and source records attributed to Shapiro, B. J..

41 records · Page 3Linked to original sources

bioRxiv2019

Two cases of type-a Haemophilus influenzae meningitis within the same week in the same hospital are phylogenetically unrelated but recently exchanged capsule genes

H. influenzae causes common and sometimes severe pediatric disease including chronic obstructive respiratory disease, otitis media, and infections of the central nervous system. Serotype b strains, with a b-type capsule, have been the historical cause of invasive disease, and the introduction of a serotype b-specific vaccine has led to their decline. However, unencapsulated or non-b-type H. influenzae infections are not prevented by the vaccine and appear to be increasing in frequency. Here we report two pediatric cases of severe central nervous system H. influenzae infection presenting to the same hospital in San Diego, California during the same week in January 2016. Due to good vaccine coverage in this part of the world, H. influenzae cases are normally rare and seeing two cases in the same week was unexpected. We thus suspected a recent transmission chain, and possible local outbreak. To test this hypothesis, we isolated and sequenced whole genomes from each patient and placed them in a phylogenetic tree spanning the known diversity of H. influenzae. Surprisingly, we found that the two isolates (H1 and H2) belonged to distantly related lineages, suggesting two independent transmission events and ruling out a local outbreak. Despite being distantly related, H1 and H2 belong to two different lineages that appear to engage in frequent horizontal gene transfer (HGT), suggesting overlapping ecological niches. Together, our comparative genomic analysis supports a scenario in which an f-type ancestor of H2 arrived in North America around 2011 and acquired an a-type capsule by recombination (HGT) with a recent ancestor of H1. Therefore, as in other bacterial pathogens, capsule switching by HGT may be an important evolutionary mechanism of vaccine evasion in H. influenzae.\n\nOUTCOMETwo cases of severe central nervous system H. influenzae infection occurred during the same week in the same hospital in San Diego, California - a region where such infections are usually very rare due to vaccine coverage. We thus suspected a local outbreak of an H. influenzae clone not covered by the vaccine. Using whole genome sequencing and phylogenetic analysis of two isolates (H1 and H2, one from each patient), we found that they were distantly related, rapidly ruling out a local outbreak and suggesting independent transmission events. This result highlights the potential for rapid global spread of non-vaccine H. influenzae strains. In this case, both H1 and H2 both encoded a-type capsules, whereas the vaccine targets b-type capsules. We also present comparative genomic evidence that a recent f-type ancestor of H2 acquired an a-type capsule locus from a recent ancestor of H1, and that this horizontal gene transfer (HGT) event likely happened in the past decade in North America, but probably not in the San Diego hospital. These results highlight the potential importance of HGT in the capsule locus in allowing H. influenzae to escape vaccine coverage.\n\nDATA SUMMARYH. influenzae H1 and H2 genome sequences have been deposited in NCBI under BioProject PRJNA534512.\n\nCONFLICT OF INTEREST STATEMENTThe authors declare that they have no conflict of interest to report.

microbiology↗

bioRxiv2019

Diversity begets diversity in microbiomes

Microbes are embedded in complex communities where they engage in a wide array of intra- and inter-specific interactions. The extent to which these interactions drive or impede microbiome diversity is not well understood. Historically, two contrasting hypotheses have been suggested to explain how species interactions could influence diversity. Ecological Controls (EC) predicts a negative relationship, where the evolution or migration of novel types is constrained as niches become filled. In contrast, Diversity Begets Diversity (DBD) predicts a positive relationship, with existing diversity promoting the accumulation of further diversity via niche construction and other interactions. Using high-throughput amplicon sequencing data from the Earth Microbiome Project, we provide evidence that DBD is strongest in low-diversity biomes, but weaker in more diverse biomes, consistent with biotic interactions initially favoring the accumulation of diversity (as predicted by DBD). However, as niches become increasingly filled, diversity hits a plateau (as predicted by EC). Impact statementMicrobiome diversity favors further diversity in a positive feedback that is strongest in lower-diversity biomes (e.g. guts) but which plateaus as niches are increasingly filled in higher-diversity biomes (e.g. soils).

evolutionary biology↗

bioRxiv2019

Coherence of Microcystis species revealed through population genomics

Microcystis is a genus of freshwater cyanobacteria which causes harmful blooms in ecosystems worldwide. Some Microcystis strains produce harmful toxins such as microcystin, impacting drinking water quality. Microcystis colony morphology, rather than genetic similarity, is often used to classify Microcystis into morphospecies. However, colony morphology is a plastic trait which can change depending on environmental and laboratory culture conditions, and is thus an inadequate criterion for species delineation. Furthermore, Microcystis populations are thought to disperse globally and constitute a homogeneous gene pool. However, this assertion is based on relatively incomplete characterization of Microcystis genomic diversity. To better understand these issues, we performed a population genomic analysis of 33 newly sequenced genomes (of which 19 were resequenced to check for mutation in culture) mainly from Canada and Brazil. We identified eight Microcystis clusters of genomic similarity, only four of which correspond to named morphospecies and monophyletic groups. Notably, M. aeruginosa is paraphyletic, distributed across four genomic clusters, suggesting it is not a coherent species. Most monophyletic groups are specific to a unique geographic location, suggesting biogeographic structure over relatively short evolutionary time scales. Higher homologous recombination rates within than between clusters further suggest that monophyletic groups might adhere to a Biological Species-like concept, in which barriers to gene flow maintain species distinctness. However, certain genes - including some involved in microcystin and micropeptin biosynthesis - are recombined between monophyletic groups in the same geographic location, suggesting local adaptation. Together, our results show the importance of using genomic criteria for Microcystis species delimitation and suggest the existence of locally adapted lineages and genes. ImportanceThe genus Microcystis is responsible for harmful and often toxic cyanobacterial blooms across the world, yet it is unclear how and if the genus should be divided into ecologically and genomically distinct species. To resolve the controversy and uncertainty surrounding Microcystis species, we performed a population genomic analysis of Microcystis genome from public databases, along with new isolates from Canada and Brazil. We inferred that significant genetic substructure exists within Microcystis, with several species being maintained by barriers to gene flow. Thus, Microcystis appears to be among a growing number of bacteria that adhere to a Biological Species-like Concept (BSC). Barriers to gene flow are permeable, however, and we find evidence for relatively frequent cross-species horizontal gene transfer (HGT) of genes that may be involved in local adaptation. Distinct clades of Microcystis (putative species) tend to have distinct profiles of toxin biosynthesis genes, and yet toxin genes are also subject to cross-species HGT and local adaptation. Our results thus pave the way for more informed classification, monitoring and understanding of harmful Microcystis blooms.

microbiology↗

bioRxiv2017

Niche separation increases with genetic distance among bloom-forming cyanobacteria

Bacterial communities are composed of distinct groups of potentially interacting lineages, each thought to occupy a distinct ecological niche. It remains unclear, however, how quickly niche preference evolves and whether more closely related lineages are more likely to share ecological niches. We addressed these questions by following the dynamics of two bloom-forming cyanobacterial genera over an 8-year time-course in Lake Champlain, Canada, using 16S amplicon sequencing and measurements of several environmental parameters. The two genera, Microcystis (M) and Dolichospermum (D), are frequently observed simultaneously during bloom events and thus have partially overlapping niches. However, the extent of their niche overlap is debated, and it is also unclear to what extent niche partitioning occurs among strains within each genus. To identify strains within each genus, we applied minimum entropy decomposition (MED) to 16S rRNA gene sequences. We confirmed that at a genus level, M and D have different preferences for nitrogen and phosphorus concentrations. Within each genus, we also identified strains differentially associated with temperature, precipitation, and concentrations of nutrients and toxins. In general, niche similarity between strains (as measured by co-occurrence over time) declined with genetic distance. This pattern is consistent with habitat filtering - in which closely-related taxa are ecologically similar, and therefore tend to co-occur under similar environmental conditions. In contrast with this general pattern, similarity in certain niche dimensions (notably particulate nitrogen and phosphorus) did not decline linearly with genetic distance, and instead showed a complex polynomial relationship. This observation suggests the importance of processes other than habitat filtering - such as competition between closely-related taxa, or convergent trait evolution in distantly-related taxa - in shaping particular traits in microbial communities.

ecology↗

bioRxiv2017

Vibrio cholerae genomic diversity within and between patients

Cholera is a severe, waterborne diarrheal disease caused by toxin-producing strains of the bacterium Vibrio cholerae. Comparative genomics has revealed \"waves\" of cholera transmission and evolution, in which clones are successively replaced over decades and centuries. However, the extent of V. cholerae genetic diversity within an epidemic or even within an individual patient is poorly understood. Here, we characterized V. cholerae genomic diversity at a micro-epidemiological level within and between individual patients from Bangladesh and Haiti. To capture within-patient diversity, we isolated multiple (8 to 20) V. cholerae colonies from each of eight patients, sequenced their genomes and identified point mutations and gene gain/loss events. We found limited but detectable diversity at the level of point mutations within hosts (zero to three single nucleotide variants within each patient), and comparatively higher gene content variation within hosts (at least one gain/loss event per patient, and up to 103 events in one patient). Much of the gene content variation appeared to be due to gain and loss of phage and plasmids within the V. cholerae population, with occasional exchanges between V. cholerae and other members of the gut microbiota. We also show that certain intra-host variants have phenotypic consequences. For example, the acquisition of a Bacteroides plasmid and nonsynonymous mutations in a sensor histidine kinase gene both reduced biofilm formation, an important trait for environmental survival. Together, our results show that V. cholerae is measurably evolving within patients, with possible implications for disease outcomes and transmission dynamics.\n\nAuthor SummaryVibrio cholerae is the etiological agent of cholera, a severe diarrheal disease endemic to Bangladesh and responsible for global outbreaks, including one ongoing in Haiti. Certain bacterial pathogens can evolve and diversify within the human host, often altering virulence and antibiotic resistance. However, most examples of within-host evolution have come from chronic infections, in which the pathogen has sufficient time to mutate and diversify, and little attention has been paid to more acute infections such as the one caused by V. cholerae. The goal of this study was to measure the extent of within-host evolution of V. cholerae within individual infected patients. By sequencing multiple bacterial isolates_from each of eight patients from Bangladesh and Haiti, we found that cholera patients can harbor a diverse population of V. cholerae. As expected for an acute infection, this diversity is limited, ranging from zero to three point mutations (single nucleotide variants) per patient. However, gene gain/loss events are more prevalent than point mutations, occurring in every single patient, and sometimes involving the transfer of dozens of genes on plasmids. Even if rare, point mutations and gene gain/loss events may be maintained by natural selection, and can alter clinically-and environmentally-relevant phenotypes such as biofilm formation. Therefore, within-patient evolution has the potential to impact clinical and epidemiological outcomes. Together, our results demonstrate that within-patient evolution may be a general feature of both acute and chronic infections, and that gene gain/loss may be an important but under-appreciated feature of within-host evolution.

microbiology↗