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Role of Legionella pneumophila Lvh TIVSS in virulence

Award Number: SC3GM136544
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Role of Legionella pneumophila Lvh TIVSS in virulence - Abstract. The Legionella genus has more than 60 species from which 20 are associated with Legionnaires’ disease, a form of atypical pneumonia. More than 90% of Legionnaires’ disease cases are caused by L. pneumophila serogroup 1. Legionella tends to colonize plumbing system biofilms and amoebae cysts which are resistant to water purification treatment. The ability of Legionella spp. to persist and multiply in amoeba and humans and cause clinical disease depends on a set of virulence genes and on the coordinate regulation of gene functions that combat the effects of innate and acquired host defenses. Therefore, the main objective of this proposal is to elucidate the molecular mechanisms that Legionella pneumophila has evolved to overcome host innate immune responses and allow it to establish an infection. The L. pneumophila genome contains clusters of genes that encode two types of type IV (TIVSS) secretion systems; lvh and dot/icm. While the genetic organization of dot/icm, and its role in virulence is well established, there is limited information about the role of Lvh TIVSS. The Legionella strains that lack Lvh TIVSS have markedly reduced cytotoxicity. Additionally, Lvh TIVSS plays an important role in host-cell infection by L. pneumophila grown at 30°C, and in the effective delay of phagosome acidification. The L. pneumophila lvh locus is required for the restoration of entry and intracellular multiplication in dot/icm mutants following incubation in water and amoeba encystment. We have demonstrated that Legionella pneumophila’s Lvh TIVSS machinery localize at cell poles, and such localization has been reported to be important for virulence in other pathogens. We also demonstrated that Lvh TIVSS is important for host-cell caspase-3/7 activation when Legionella strains are grown under 30°C. Based on our preliminary data and data from the literature, our central hypothesis is that Lvh contributes to Legionella virulence under infection from the environment and regulates late stages of cellular infection and further dissemination of bacteria. We will test our central hypothesis and attain our objective by evaluating the role of Lvh TIVSS in the modulation of host cell immunity, gene expression, and programmed cell death. Revealing Lvh functions will uncover sites of potential weakness in bacterial pathogens that may be exploited for therapeutic intervention, development of rational, optimally efficacious vaccines, and disease control. Thus, the main goal of this project is to understand how the host-cell immune system recognizes microbial virulence factors during infection, produces a protective response, and the mechanism by which Legionella Lvh can inhibit this protective response. The results from this work will have an important positive impact on human health because they will provide important information about pathways or networks altered by L. pneumophila Lvh TIVSS in the host, which may lay the groundwork for the development of a new class of targeted treatments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $105,000 )
2024	2024	SOUTHERN UNIVERSITY AND A & M COLLEGE	730 HARDING BLVD	BATON ROUGE	LA	70807	EAST BATON ROUGE	USA	Biomedical Research and Research Training	000	4	5/15/2024	NON-COMPETING CONTINUATION	$105,000
														Subtotal = $105,000

Issue Date FY: 2023 ( Subtotal = $105,000 )
2023	2023	SOUTHERN UNIVERSITY AND A & M COLLEGE	730 HARDING BLVD	BATON ROUGE	LA	70807	EAST BATON ROUGE	USA	Biomedical Research and Research Training	000	3	5/25/2023	NON-COMPETING CONTINUATION	$105,000
														Subtotal = $105,000

Issue Date FY: 2022 ( Subtotal = $102,600 )
2022	2022	SOUTHERN UNIVERSITY AND A & M COLLEGE	730 HARDING BLVD	BATON ROUGE	LA	70807	EAST BATON ROUGE	USA	Biomedical Research and Research Training	000	2	5/19/2022	NON-COMPETING CONTINUATION	$102,600
														Subtotal = $102,600

Issue Date FY: 2021 ( Subtotal = $102,460 )
2021	2021	SOUTHERN UNIVERSITY AND A & M COLLEGE	730 HARDING BLVD	BATON ROUGE	LA	70807	EAST BATON ROUGE	USA	Biomedical Research and Research Training	000	1	8/20/2021	NEW	$102,460
														Subtotal = $102,460

Grand Total All Awards = $415,060

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Role of Legionella pneumophila Lvh TIVSS in virulence

Award Number: SC3GM136544

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/20/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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