Spinola Lab

The research lab of Stanley M. Spinola, MD focuses on the bacterium Haemophilus ducreyi, which causes cutaneous ulcers in children in the tropics and the genital ulcer disease chancroid, which facilitates the transmission of HIV-1. The laboratory developed a model in which human volunteers are infected on the skin of the arm with the bacterium that is relevant to both syndromes. Features of the model include a low dose required for infection (1 to 100 CFU) and a clinical course and a cutaneous immune response that mimics naturally occurring disease.

Active Research

In both experimental and natural infection, H. ducreyi resides in an abscess, and the primary mechanism by which the organism causes disease is evasion of phagocytosis. One major project in the laboratory is to determine the molecular interaction network between H. ducreyi and the host on a transcriptional level using RNA-sequencing; preliminary data indicate that H. ducreyi is primarily seeking nutrients such as ascorbic acid and adapting to anaerobiosis in vivo.

Another major project is to try to understand how H. ducreyi causes leg ulcers in children and by microbiome analysis discover other agents that cause this syndrome. The laboratory found that activation of a two-component system cripples the virulence of H. ducreyi and Neisseria gonorrhoeae in vivo. Investigators have identified small molecules that activate this system as potential antimicrobials.

Research Funding

Indiana CTSI TRAC1 PDT Pilot Grant Mechanism. Project Period: 11/01/14-10/31/17.
The goal of this pilot grant is to perform medicinal chemistry on a nitroindole that activates the CpxRA system in Escherichia coli to address potential toxicity issues and to do preclinical testing of optimized compounds in a murine model of urinary tract infection
Role: Principal Investigator

Indiana CTSI – Indiana Drug Discovery Alliance. Project Period: 12/01/14-11/31/17
The goal of this pilot grant is to screen 30,000 compounds from a small molecule library to find new leads that activate the CpxRA system in Escherichia coli
Role: Principal Investigator

Recent Publications

A full list of Stanley M. Spinola, MD publication history is available on PubMed.

Houinei W, Godornes C, Kapa A, Mooring EQ, González-Beiras C, Knauf S, Watup R, Paru R, Advent P, Bieb S, Sanz S, Spinola SM, Lukehart SA, Mitjà O. Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea. PLoS Negl Trop Dis. 2017 May 10;11(5):e0004958. doi: 10.1371/journal.pntd.0004958. PMCID: PMC5425006

Gangaiah D, Raterman EL, Wu H, Fortney KR, Gao H, Liu Y, Jerse AE, Spinola SM. Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection. Infection and immunity. 2017;85(9). doi: 10.1128/IAI.00307-17. PubMed PMID: 28652307.

Gangaiah D, Marinov GK, Roberts SA, Robson J, Spinola SM. Draft whole-genome sequence of the Haemophilus ducreyi strain AUSPNG1 isolated from a cutaneous ulcer of a child from Papua New Guinea. Genome Announc. 2016 Feb 4;4(1). pii: e01661-15. doi: 10.1128/genomeA.01661-15. PMCID: PMC4742684

Gangaiah D, Zhang X, Baker B, Fortney KR, Holley C, Munson, RS, Jr., Liu Y, Spinola SM. Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers. Infect. Immun. 2016; 84: 1514-1525. PMCID: PMC4862733

Singer M, Li W, Morré SA, Ouburg S, Spinola, SM. Host polymorphisms in TLR9 and IL10 are associated with the outcomes of experimental Haemophilus ducreyi infection in human volunteers. J. Infect. Dis. 2016; 214: 489-95. PMCID: PMC4936646

Gangaiah D, Spinola SM. Haemophilus ducreyi cutaneous ulcer strains diverged from both class I and class II genital ulcer strains: implications for epidemiological studies. PLoS Negl. Trop. Dis.2016 Dec 27;10(12):e0005259. doi: 10.1371/journal.pntd.0005259. PMCID: PMC5222509

van Rensburg JJ, Fortney KR, Chen L, Kreiger A, Lima BP, Wolfe AJ, Katz BP, Zhang Z-Y, Spinola SM. Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system. Antimicrob Agents Chemother. 2015; 59: 3789-3799. PMCID: PMC25870061

Gangaiah D, Webb KM, Humphreys TL, Fortney KR, Toh E, Tai A, Katz SS, Pillay A, Chen C-Y, Roberts SA, Munson, RS, Jr., Spinola SM. Haemophilus ducreyi cutaneous ulcer strains are nearly identical to Class I genital ulcer strains. PLoS Neglected Tropical Diseases 2015; July 6; 9(7): e0003918. PMCID: PMC4492979

Holley C, Zhang X, Fortney KR, Ellinger S, Johnson P, Baker B, Liu Y, Janowicz DM, Katz BP, Munson, RS, Jr., Spinola SM. DksA and (p)ppGpp have unique and overlapping contributions to Haemophilus ducreyi pathogenesis in humans. Infect. Immun. 2015; 83: 3281-3292. PMCID: PMC4496623

*van Rensburg JJ, Lin H, Gao X, Toh E, Fortney KR, Ellinger S, Zwickl B, Janowicz DM, Katz BP, Nelson DE, Dong Q, Spinola SM. The human skin microbiome associates with the outcome of and is influenced by bacterial infection. mBio. 2015;6(5). doi: 10.1128/mBio.01315-15. PMCID: PMC4600114           *Featured in The Scientist, 9/6/15, mBiosphere 9/15/15, and Microbe 2015. 10: 411

Faculty Research Team

Stanley M. Spinola, MD

Stanley M. Spinola, MD

Chair, Department of Microbiology & Immunology

Additional Research Team Members

There is currently one technician in the laboratory (Kate Fortney). New trainees are exposed to molecular biology, immunology, cell biology, microbiome research, therapeutics, and the methods and ethics of human research.