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Becker, M. E.

Publications and source records attributed to Becker, M. E..

2 recordsLinked to original sources

Vibrio cholerae alkalizes its environment via citrate metabolism to inhibit enteric growth

Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in both marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources such as chitin and citrate. We observed that when V. cholerae strains were grown on a medium with citrate, the mediums chemical composition turned into a hostile alkaline environment for Gram-negative bacteria such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae citrate metabolism mutants {Delta}oadA-1, {Delta}citE, and {Delta}citF mutants were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria.

microbiology↗

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

The systemic nature of SARS-CoV-2 infection is highly recognized, but poorly characterized. A non-invasive and unbiased method is needed to clarify whole body spatiotemporal dynamics of SARS-CoV-2 infection after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of three rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we track the 64Cu-labelled CR3022-F(ab)2 probe targeting the spike protein of SARS-CoV-2 to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Using this method, we uncovered differences in lung pathology between infection with the WA1 isolate and the delta variant, which were readily corroborated through computed tomography scans. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites. Graphic AbstractPET/CT detected SARS-CoV-2 infection of 4 different tissues in the male genital tract illuminates the cause of COVID-19 clinical sequalae of male sexual health and fertility O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/481974v2_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@188c53aorg.highwire.dtl.DTLVardef@4c639forg.highwire.dtl.DTLVardef@120799forg.highwire.dtl.DTLVardef@110edb1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Diagram shows schematic illustration of the male genital tract of the rhesus macaque. Virus icon shows sites of SARS-CoV-2 PET signal. Text highlighting the clinical sequalae associated with each sight of infection is shown in text adjacent to each infection site. C_FIG

immunology↗