Magdalene Yh So

Interests

Research

Bacterial genetics and mechanisms of pathogenesis.

Teaching

I co-organize IMB565, a graduate course that focuses on how microbes interact with their hosts to cause infection. In my section of the course, which spans 6+ weeks, I cover current topics in bacteriology.

Courses

Scholarly Contributions

Chapters

• Biais, N., Higashi, D. L., So, M. Y., & Ladoux, B. (2012). Techniques to Measure Pilus Retraction Forces. In Methods in Molecular Biology(pp 197-216). Springer Science and Business Media LLC2012. doi:10.1007/978-1-61779-346-2_13

Journals/Publications

• Rendón, M. A., Lona, B., Ma, M., & So, M. (2019). RpoN and the Nps and Npa two-component regulatory system control pilE transcription in commensal Neisseria. MicrobiologyOpen, 8(5), e00713.
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  Over 20 genes are involved in the biogenesis and function of the Neisseria Type IV pilus (Tfp). In the pathogenic species, RpoD and the integration host factor (IHF) protein regulate expression of pilE, encoding the Tfp structural subunit. We previously reported that in commensal species, pilE transcription is regulated by RpoN, IHF, and activator Npa. Npa has many hallmarks of response regulators in two-component regulatory systems, leading us to search for its response regulator partner. We report that Npa partners with sensor kinase Nps to control pilE transcription. Among the genes involved in Tfp biogenesis and function, only pilE is controlled by RpoN and Npa/Nps. We summarize our findings in a model, and discuss the implications of the differential regulation of pilE the context of Neisseria Tfp biogenesis.
• Rhodes, K., Ma, M., & So, M. (2019). A Natural Mouse Model for Neisseria Persistent Colonization. Methods in molecular biology (Clifton, N.J.), 1997, 403-412.
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  We have developed a natural mouse model to study persistent colonization by commensal Neisseria. The system couples the ordinary lab mouse with Neisseria musculi (Nmus), a commensal in the oral cavity and gut of the wild mouse, Mus musculus. The pairing of Nmus with its natural reservoir circumvents host restriction barriers that have impeded previous studies of Neisseria in vivo behavior. The model allows, for the first time, for the dissection of host and neisserial determinants of asymptomatic colonization. Inoculation procedures are noninvasive and susceptibility to Nmus colonization varies with host genetic background. In colonized mice, bacterial burdens are detectable up to 1-year post inoculation, making it an ideal model for the study of persistence. As Nmus encodes several Neisseria gonorrhoeae (and Neisseria meningitidis) host interaction factors, the system can be used to query the in vivo functions of these commonly held genes and factors. Nmus also encodes many pathogenic Neisseria vaccine targets including a polysaccharide capsule, making the model potentially useful for vaccine development. The ease of genetic manipulation of Nmus enhances the feasibility of such studies.
• Hockenberry, A. M., Post, D. M., Rhodes, K. A., Apicella, M., & So, M. (2018). Perturbing the acetylation status of the Type IV pilus retraction motor, PilT, reduces Neisseria gonorrhoeae viability. Molecular microbiology, 110(5), 677-688.
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  Post-translational acetylation is a common protein modification in bacteria. It was recently reported that Neisseria gonorrhoeae acetylates the Type IV pilus retraction motor, PilT. Here, we show recombinant PilT can be acetylated in vitro and acetylation does not affect PilT ultrastructure. To investigate the function of PilT acetylation, we mutated an acetylated lysine, K117, to mimic its acetylated or unacetylated forms. These mutations were not tolerated by wild-type N. gonorrhoeae, but they were tolerated by N. gonorrhoeae carrying an inducible pilE when grown without inducer. We identified additional mutations in pilT and pilU that suppress the lethality of K117 mutations. To investigate the link between PilE and PilT acetylation, we found the lack of PilE decreases PilT acetylation levels and increases the amount of PilT associated with the inner membrane. Finally, we found no difference between wild-type and mutant cells in transformation efficiency, suggesting neither mutation inhibits Type IV pilus retraction. Mutant cells, however, form microcolonies morphologically distinct from wt cells. We conclude that interfering with the acetylation status of PilT greatly reduces N. gonorrhoeae viability, and mutations in pilT, pilU and pilE can overcome this lethality. We discuss the implications of these findings in the context of Type IV pilus retraction regulation.
• Ma, M., Powell, D. A., Weyand, N. J., Rhodes, K. A., Rendón, M. A., Frelinger, J. A., & So, M. (2018). A Natural Mouse Model for Neisseria Colonization. Infection and immunity, 86(5).
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  Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, , with the laboratory mouse. The pairing of a mouse commensal with its natural host circumvents issues of host restriction. Studies are performed in the absence of antibiotics, hormones, invasive procedures, or genetic manipulation of the host. A single dose of , administered orally, leads to long-term colonization of the oral cavity and gut. All mice are healthy. Susceptibility to colonization is determined by host genetics and innate immunity. For , colonization requires the type IV pilus. Reagents and powerful tools are readily available for manipulating the laboratory mouse, allowing easy dissection of host determinants controlling colonization resistance. is genetically related to human-dwelling commensal and pathogenic and encodes host interaction factors and vaccine antigens of pathogenic Our system provides a natural approach for studying -host interactions and is potentially useful for vaccine efficacy studies.
• So, M. Y. (2018). The commensal Neisseria musculi modulates host innate immunity to promote oral colonization.. ImmunoHorizons.
• Weyand, N. J., Wertheimer, A. M., Hobbs, T. R., Sisko, J. L., Taku, N. A., Gregston, L. D., Clary, S., Higashi, D. L., Biais, N., Brown, L. M., Planer, S. L., Legasse, A. W., Axthelm, M. K., Wong, S. W., & So, M. Y. (2013). Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer. PNAS, 110(8).
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  The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe-host interactions. We developed a rhesus macaque model for studying Neisseria-host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates.
• Choilean, S. N., Weyand, N. J., Neumann, C., Thomas, J., & So, M. Y. (2011). The dynamic processing of CD46 intracellular domains provides a molecular rheostat for T cell activation.. PLoS One, 16:e16287.
• Higashi, D. L., Biais, N., Weyand, N. J., Agellon, A., Sisko, J. L., Brown, L. M., & So, M. Y. (2011). N. elongata produces type IV pili that mediate interspecies gene transfer with N. gonorrhoeae. PloS One, 6(6).
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  The genus Neisseria contains at least eight commensal and two pathogenic species. According to the Neisseria phylogenetic tree, commensals are basal to the pathogens. N. elongata, which is at the opposite end of the tree from N. gonorrhoeae, has been observed to be fimbriated, and these fimbriae are correlated with genetic competence in this organism. We tested the hypothesis that the fimbriae of N. elongata are Type IV pili (Tfp), and that Tfp functions in genetic competence. We provide evidence that the N. elongata fimbriae are indeed Tfp. Tfp, as well as the DNA Uptake Sequence (DUS), greatly enhance N. elongata DNA transformation. Tfp allows N. elongata to make intimate contact with N. gonorrhoeae and to mediate the transfer of antibiotic resistance markers between these two species. We conclude that Tfp functional for genetic competence is a trait of a commensal member of the Neisseria genus. Our findings provide a mechanism for the horizontal gene transfer that has been observed among Neisseria species.
• Biais, N., Higashi, D. L., Brujic, J., So, M. Y., & Sheetz, M. P. (2010). Force dependent polymorphism in Type IV pili reveals hidden epitopes.. PNAS, 107, 11358-11363.
• So, M., So, M. Y., Marri, P. R., Paniscus, M., Weyand, N. J., Rendón, M. A., Calton, C. M., Hernández, D. R., Higashi, D. L., Sodergren, E., Weinstock, G. M., & Rounsley, S. D. (2010). Genome sequencing reveals widespread virulence gene exchange among human Neisseria species. PloS One, 5(7).
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  Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange.
• Dietrich, M., Mollenkopf, H., So, M. Y., & Friedrich, A. (2009). Pilin regulation in the pilT mutant of Neisseria gonorrhoeae strain MS11.. FEBS Journal, 296, 248–256.
• Higashi, D. D., Zhang, G. H., Biais, N., Myers, L. R., Weyand, N. J., Elliott, D. A., & So, M. Y. (2009). Influence of Type IV pilus retraction on the architecture of the N. gonorrhoeae-infected cell cortex.. Microbiology, 155, 4084-4092.