About

James McClurg Slauch is a Professor and Head of Microbiology at the University of Illinois, with additional professorships in Biomedical and Translational Sciences and affiliation with the Carl R. Woese Institute for Genomic Biology. He holds a B.S. in Biochemistry from The Pennsylvania State University (1984), a Ph.D. in Molecular Biology from Princeton University (1990), and completed postdoctoral training in Microbiology at Harvard Medical School (1990-1993). His research focuses on the molecular mechanisms of Salmonella pathogenesis, particularly how Salmonella circumvents the host immune system to cause disease. Salmonella Typhimurium serves as a model organism in his studies due to its well-defined genetics and the availability of an excellent animal infection model. His work has elucidated the complex regulatory circuitry controlling the Type III Secretion System (T3SS) encoded on Salmonella Pathogenicity Island 1 (SPI1), which is critical for intestinal invasion and inflammatory diarrhea. This model integrates various environmental signals to explain the timing and location of T3SS machinery production in the host intestine, representing a significant advance in understanding Salmonella pathogenesis. Professor Slauch's research also addresses the mechanisms by which Salmonella survives extraintestinal infections, particularly its ability to persist within macrophages despite the oxidative burst that normally kills bacteria. His studies challenge the prevailing view by demonstrating that phagocytic superoxide targets extracytoplasmic components rather than bacterial DNA or cytoplasmic molecules. Using innovative genetic approaches such as differential TnSeq, his lab identifies genes interacting with oxidative stress resistance factors like sodC I, including those involved in polyamine transport and outer membrane assembly. Notably, his work on the tamAB locus reveals its induction by the PhoPQ regulon during macrophage infection and its role in outer membrane homeostasis under phagosomal stress, contributing to Salmonella virulence. Through these investigations, Slauch aims to uncover the physiological basis of bacterial sensitivity to host defenses and the adaptations that enable pathogen survival and virulence.

Research topics

• Cell biology
• Biology
• Genetics
• Biochemistry
• Immunology
• Microbiology
• Cancer research

Selected publications

• The CorC proteins MgpA (YoaE) and CorC protect from excess-cation stress and are required for egg white tolerance and virulence in <i>Salmonella</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-18

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Cation homeostasis is a vital function. In Salmonella , growth in very low Mg 2+ induces expression of high-affinity Mg²⁺ transporters and synthesis of polyamines, organic cations that substitute for Mg²⁺. Once Mg²⁺ levels are re-established, the polyamines must be excreted by PaeA. Otherwise, cells lose viability due to a condition we term excess-cation stress. We sought additional tolerance mechanisms for this stress. We show that CorC and MgpA (YoaE) are essential for survival in stationary phase after Mg 2+ starvation. Deletion of corC causes a loss of viability additive with the paeA phenotype. Deletion of mgpA causes a synthetic defect in the corC background. This lethality is suppressed by loss of the inducible Mg 2+ transporters, suggesting that the corC mgpA mutant is sensitive to changes in intracellular Mg 2+ . CorC and MgpA function independently of PaeA. A paeA mutant is sensitive to externally added polyamine in stationary phase; loss of CorC and MgpA suppressed this sensitivity. Conversely, the corC mgpA mutant, but not the paeA mutant, exhibited sensitivity to high Mg 2+ and egg white. The corC mgpA mutant is also attenuated in a mouse model. The corC and mgpA genes are induced in response to increased Mg 2+ concentrations. Thus, CorC and MgpA play some interrelated role in cation homeostasis. It is unlikely that these phenotypes are due to absolute levels of cations. Rather, the cell maintains relative concentrations of various cations that likely compete for binding to anionic components. Imbalance of these cations affects some essential function(s), leading to a loss of viability. IMPORTANCE Mg²⁺ and other cations are critical for counteracting anionic compounds in the cell including RNA, DNA, and nucleotides. Both excessively low and high cation levels are toxic. To maintain proper intracellular concentrations, cells must regulate Mg²⁺ importers and exporters, or modulate the levels of other cations or anions that affect free Mg²⁺ levels. In Salmonella , no mutants sensitive to high Mg²⁺ levels have been identified. Here, we demonstrate that the largely uncharacterized proteins MgpA and CorC are induced under high Mg²⁺ conditions and are essential for tolerance to high Mg²⁺ levels. These genes are also essential for survival during endogenous excess-cation stress triggered by the transition to stationary phase after Mg²⁺ starvation, as well as for virulence, highlighting the broader role of cation homeostasis.

  PublisherOA PDFDOI

• The <i>Salmonella</i> pathogenicity island 1-encoded small RNA InvR mediates post-transcriptional feedback control of the activator HilA in <i>Salmonella</i>

  Journal of Bacteriology · 2025-02-27 · 4 citations

  articleOpen access

  ABSTRACT Salmonella Pathogenicity Island 1 (SPI1) encodes a Type-3 secretion system (T3SS) essential for Salmonella invasion of intestinal epithelial cells. Many environmental and regulatory signals control SPI1 gene expression, but in most cases, the molecular mechanisms remain unclear. Many regulatory signals control SPI1 at a post-transcriptional level, and we have identified a number of small RNAs (sRNAs) that control the SPI1 regulatory circuit. The transcriptional regulator HilA activates the expression of the genes encoding the SPI1 T3SS structural and primary effector proteins. Transcription of hilA is controlled by the AraC-like proteins HilD, HilC, and RtsA. The hilA mRNA 5′ untranslated region (UTR) is ~350 nucleotides in length and binds the RNA chaperone Hfq, suggesting it is a likely target for sRNA-mediated regulation. We used rGRIL-seq (reverse global sRNA target identification by ligation and sequencing) to identify sRNAs that bind to the hilA 5′ UTR. The rGRIL-seq data, along with genetic analyses, demonstrate the SPI1-encoded sRNA inv asion gene-associated R NA (InvR) base pairs at a site overlapping the hilA ribosome binding site. HilD and HilC activate both invR and hilA . InvR, in turn, negatively regulates the translation of the hilA mRNA. Thus, the SPI1-encoded sRNA InvR acts as a negative feedback regulator of SPI1 expression. Our results suggest that InvR acts to fine-tune SPI1 expression and prevents overactivation of hilA expression, highlighting the complexity of sRNA regulatory inputs controlling SPI1 and Salmonella virulence. IMPORTANCE Salmonella Typhimurium infections pose a significant public health concern, leading to illnesses that range from mild gastroenteritis to severe systemic infection. Infection requires a complex apparatus that the bacterium uses to invade the intestinal epithelium. Understanding how Salmonella regulates this system is essential for addressing these infections effectively. Here, we show that the small RNA (sRNA) InvR imposes a negative feedback regulation on the expression of the invasion system. This work underscores the role of sRNAs in Salmonella 's complex regulatory network, offering new insights into how these molecules contribute to bacterial adaptation and pathogenesis.

  PublisherDOI

• The CorC proteins MgpA (YoaE) and CorC protect from excess-magnesium stress and are required for egg white tolerance and virulence in <i>Salmonella</i>

  mBio · 2025-08-18

  articleOpen accessSenior author

  ABSTRACT Cation homeostasis is a vital function. In Salmonella , growth in very low Mg 2+ induces expression of high-affinity Mg² + transporters and the synthesis of polyamines, organic cations that substitute for Mg² + . Once Mg² + levels are re-established, the polyamines must be excreted by PaeA. Otherwise, cells lose viability due to a condition we term excess-cation stress. We sought additional tolerance mechanisms for this stress. We show that CorC and MgpA (YoaE) are essential for survival in stationary phase after Mg 2+ starvation. Deletion of corC causes a loss of viability that is additive with the paeA phenotype. Deletion of mgpA causes a synergistic defect in the corC background. This lethality is suppressed by the loss of the inducible Mg 2+ transporters, showing that the corC mgpA mutant is sensitive to changes in intracellular Mg 2+ . CorC and MgpA function independently of PaeA. A paeA mutant is sensitive to externally added polyamine in stationary phase, while the loss of CorC and MgpA suppressed this sensitivity. Conversely, the corC mgpA mutant, but not the paeA mutant, exhibited sensitivity to high Mg 2+ and egg white. The corC mgpA mutant is also attenuated in a mouse model. The corC and mgpA genes are induced in response to increased Mg 2+ concentrations. Thus, CorC and MgpA have overlapping roles in cation homeostasis, most probably acting to efflux excess Mg 2+ . Our data suggest that cells maintain relative concentrations of various cations that likely compete for binding to anionic components. The imbalance of these cations affects some essential function(s), leading to a loss of viability. IMPORTANCE Mg² + and other cations are critical for counteracting anionic compounds in the cell including RNA, DNA, and nucleotides. Both excessively low and excessively high cation levels are toxic. To maintain proper intracellular concentrations, cells must regulate Mg² + importers and exporters or modulate the levels of other cations or anions that affect free Mg² + levels. In Salmonella , no mutants sensitive to high Mg² + levels have been identified. Here, we demonstrate that the largely uncharacterized proteins MgpA and CorC are induced under high Mg² + conditions and are essential for tolerance to high Mg² + levels. These genes are also essential for survival during endogenous excess-cation stress triggered by the transition to stationary phase after Mg² + starvation, as well as for virulence, highlighting the broader role of cation homeostasis.

  PublisherDOI

• The <i>Salmonella</i> pathogenicity island 1-encoded small RNA InvR mediates post-transcriptional feedback control of the activator HilA in <i>Salmonella</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-22 · 2 citations

  preprintOpen access

  ABSTRACT Salmonella Pathogenicity Island 1 (SPI1) encodes a type three secretion system (T3SS) essential for Salmonella invasion of intestinal epithelial cells. Many environmental and regulatory signals control SPI1 gene expression, but in most cases, the molecular mechanisms remain unclear. Many of these regulatory signals control SPI1 at a post-transcriptional level and we have identified a number of small RNAs (sRNAs) that control the SPI1 regulatory circuit. The transcriptional regulator HilA activates expression of the genes encoding the SPI1 T3SS structural and primary effector proteins. Transcription of hilA is controlled by the AraC-like proteins HilD, HilC, and RtsA. The hilA mRNA 5’ untranslated region (UTR) is ~350-nuclotides in length and binds the RNA chaperone Hfq, suggesting it is a likely target for sRNA-mediated regulation. We used the rGRIL-seq (reverse global sRNA target identification by ligation and sequencing) method to identify sRNAs that bind to the hilA 5’ UTR. The rGRIL-seq data, along with genetic analyses, demonstrate that the SPI1-encoded sRNA InvR base pairs at a site overlapping the hilA ribosome binding site. HilD and HilC activate both invR and hilA . InvR in turn negatively regulates the translation of the hilA mRNA. Thus, the SPI1-encoded sRNA InvR acts as a negative feedback regulator of SPI1 expression. Our results suggest that InvR acts to fine-tune SPI1 expression and prevent overactivation of hilA expression, highlighting the complexity of sRNA regulatory inputs controlling SPI1 and Salmonella virulence. IMPORTANCE Salmonella Typhimurium infections pose a significant public health concern, leading to illnesses that range from mild gastroenteritis to severe systemic infection. Infection is initiated and requires a complex apparatus that the bacterium uses to invade the intestinal epithelium. Understanding how Salmonella regulates this system is essential for addressing these infections effectively. Here we show that the small RNA (sRNA) InvR imposes negative feedback regulation on expression of the invasion system. This work underscores the role of sRNAs in Salmonella’s complex regulatory network, offering new insights into how these molecules contribute to bacterial adaptation and pathogenesis.

  PublisherOA PDFDOI

• Supplementary Methods, Figure Legend from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer

  2023-04-03

  preprintOpen access

  &lt;p&gt;PDF file - 122K&lt;/p&gt;

  PublisherDOI

• Supplementary Methods, Figure Legend from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer

  2023-04-03

  preprintOpen access

  &lt;p&gt;PDF file - 122K&lt;/p&gt;

  PublisherOA PDFDOI

• Data from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer

  2023-04-03

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;Immunogenic tumors grow progressively even when heavily infiltrated by CD8&lt;sup&gt;+&lt;/sup&gt; T cells. We investigated how to rescue CD8&lt;sup&gt;+&lt;/sup&gt; T-cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1&lt;sup&gt;+&lt;/sup&gt; tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells that were dysfunctional. Treatment with αPD-L1– and αCTLA-4–blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using &lt;i&gt;Salmonella&lt;/i&gt; Typhimurium A1-R (A1-R) to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T-cell response: Proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1-blocking antibody enhanced the expansion of tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells and resulted in 80% tumor rejection. Collectively, these data show a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells and eradicate advanced immunogenic tumors. &lt;i&gt;Cancer Immunol Res; 1(2); 123–33. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• TamAB is regulated by PhoPQ and functions in outer membrane homeostasis during <i>Salmonella</i> pathogenesis

  Journal of Bacteriology · 2023-09-20 · 13 citations

  articleOpen accessSenior author

  ABSTRACT Salmonella survive and replicate in macrophages, which normally kill bacteria by exposing them to a variety of harsh conditions and antimicrobial effectors, many of which target the bacterial cell envelope. The PhoPQ two-component system responds to the phagosome environment and induces factors that protect the outer membrane, allowing adaptation and growth in the macrophage. We show that PhoPQ induces the transcription of the tamAB operon both in vitro and in macrophages. The TamA protein is structurally similar to BamA, an essential protein in the Bam complex that assembles β-barrel proteins in the outer membrane, while TamB is an AsmA-family protein implicated in lipid transport between the inner and outer membranes. We show that the Bam machinery is stressed in vitro under low Mg 2+ , low pH conditions that mimic the phagosome. Not surprisingly, mutations affecting Bam function confer significant virulence defects. Although loss of TamAB alone confers no virulence defect, a tamAB deletion confers a synthetic phenotype in bam mutant backgrounds in animals and macrophages, and in vitro upon treatment with vancomycin or sodium dodecyl sulfate. Mutations affecting YhdP, which functions in partial redundancy with TamB, also confer synthetic phenotypes with bam mutations in the animal, but this interaction is not evident in vitro . Thus, in the harsh phagocytic environment of the macrophage, the outer membrane Bam machinery is compromised, and the TamAB system, and perhaps other PhoPQ-regulated factors, is induced to compensate. It is most likely that TamAB and other systems assist the Bam complex indirectly by affecting outer membrane properties. IMPORTANCE The TamAB system has been implicated in both outer membrane protein localization and phospholipid transport between the inner and outer membranes. We show that the β-barrel protein assembly complex, Bam, is stressed under conditions thought to mimic the macrophage phagosome. TamAB expression is controlled by the PhoPQ two-component system and induced in macrophages. This system somehow compensates for the Bam complex as evidenced by the fact that mutations affecting the two systems confer synthetic phenotypes in animals, macrophages, and in vitro in the presence of vancomycin or SDS. This study has implications concerning the role of TamAB in outer membrane homeostasis. It also contributes to our understanding of the systems necessary for Salmonella to adapt and reproduce within the macrophage phagosome.

  PublisherOA PDFDOI

• Supplementary Figures 1 - 3 from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer

  2023-04-03

  preprintOpen access

  &lt;p&gt;PDF file - 291K, Figure S1. A1-R SIINF preferentially accumulates in established B16-OVA tumors. Figure S2. A1-R SIINF induces systemic SIINF-specific CD8+ T cell proliferation. Figure S3. Weekly A1-R SIINF treatment leads to rejection of established B16-OVA tumors. Figure S4. The majority of intratumoral SIINF-specific CD8+ T cells still express a high level of PD-1 following A1-R OVA treatment.&lt;/p&gt;

  PublisherDOI

• Supplementary Figures 1 - 3 from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer

  2023-04-03

  preprintOpen access

  &lt;p&gt;PDF file - 291K, Figure S1. A1-R SIINF preferentially accumulates in established B16-OVA tumors. Figure S2. A1-R SIINF induces systemic SIINF-specific CD8+ T cell proliferation. Figure S3. Weekly A1-R SIINF treatment leads to rejection of established B16-OVA tumors. Figure S4. The majority of intratumoral SIINF-specific CD8+ T cells still express a high level of PD-1 following A1-R OVA treatment.&lt;/p&gt;

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21AI037530

  NIH · $130k · 1997

• NIH Grant R01GM120182

  NIH · $1.2M · 2021

• NIH Grant R01AI080705

  NIH · $1.4M · 2014

• NIH Grant R01AI063230

  NIH · $1.7M · 2010

• NIH Grant R21AI111455

  NIH · $419k · 2016

Frequent coauthors

• Donald A. Rowley

  University of Chicago

  70 shared

• David H. Munn

  Augusta University Health

  70 shared

• Theodore Karrison

  University of Chicago

  70 shared

• Byron Burnette

  70 shared

• Ming Zhao

  Sun Yat-sen University Cancer Center

  64 shared

• Hans Schreiber

  University of Chicago

  62 shared

• Christian Idel

  62 shared

• Yang‐Xin Fu

  Tsinghua University

  62 shared

Education

• M.D.

  Carle Illinois College of Medicine

Awards & honors

• Carle Illinois College of Medicine Professorships, Awards, a…