2. Academic Validation
  3. GaSal-2: A Water-Soluble Antipseudomonal Agent Targeting the Extracellular Hemophore HasAp

GaSal-2: A Water-Soluble Antipseudomonal Agent Targeting the Extracellular Hemophore HasAp

  • ACS Infect Dis. 2025 Aug 8;11(8):2287-2300. doi: 10.1021/acsinfecdis.5c00296.
Aziza Frank 1,  Lucia Hwang 1,  William T Witt 2,  Garrick Centola 1,  Kieran Johnson 1,  Yong Ai 1,  Emel Sen-Kilic 2,  Gage M Pyles 2,  Annalisa B Huckaby 2,  Catherine B Blackwood 2,  Sarah Jo Miller 2,  S Matthew Hudson 2,  Kellie Hom 1,  Wenbo Yu 1,  Alexander D MacKerell Jr 1 3,  Mariette Barbier 2,  Angela Wilks 1 3,  Fengtian Xue 1 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, United States.
  • 2 West Virginia University Vaccine Development Center, Department of Microbiology, Immunology and Cell Biology. Morgantown, West Virginia 26505, United States.
  • 3 Computer-Aided Drug Design Center, University of Maryland, Baltimore, Maryland 2120, United States.
PMID: 40731254 DOI: 10.1021/acsinfecdis.5c00296
Abstract

Multidrug-resistant Pseudomonas aeruginosa is a critical pathogen that demands new Antibiotics. During P. aeruginosa Infection, the extracellular hemophore hasAp and its outer membrane receptor hasR are the most dramatically upregulated genes. The P. aeruginosa ΔhasR strain exhibits significantly reduced growth and virulence. We previously described a gallium salophen complex GaSal that demonstrated antipseudomonal potential by targeting HasAp. Here, we report the development of a water-soluble derivative, GaSal-2, which tightly binds to HasAp, blocks transcriptional activation of the Bacterial cell surface signaling cascade, inhibits P. aeruginosa growth, and effectively disrupts P. aeruginosa established biofilms. Moreover, GaSal-2 is not toxic to human lung fibroblasts and hepatocytes. It has shown promising antipseudomonal effects in a murine lung Infection model.

Keywords

Pseudomonas aeruginosa; biofilms; extracellular hemophore; gallium complex; heme acquisition.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z