TY - JOUR
T1 - Protective Action of Linear Polyethylenimine against Staphylococcus aureus Colonization and Exaggerated Inflammation in Vitro and in Vivo
AU - Mayandi, Venkatesh
AU - Sridhar, Sreepathy
AU - Fazil, Mobashar Hussain Urf Turabe
AU - Goh, Eunice Tze Leng
AU - Htoon, Hla Myint
AU - Orive, Gorka
AU - Choong, Yeu Khai
AU - Saravanan, Rathi
AU - Beuerman, Roger W.
AU - Barkham, Timothy Mark Sebastian
AU - Yang, Liang
AU - Baskaran, Mani
AU - Jhanji, Vishal
AU - Loh, Xian Jun
AU - Verma, Navin Kumar
AU - Lakshminarayanan, Rajamani
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/8/9
Y1 - 2019/8/9
N2 - Increased evolution of multidrug resistant pathogens necessitates the development of multifunctional antimicrobials. There is a perceived need for developing new antimicrobials that can interfere with acute inflammation after bacterial infections. Here, we investigated the therapeutic potential of linear polyethylenimine (LPEI) in vitro and in vivo. The minimum inhibitory concentration of LPEI ranged from 8 to 32 μg/mL and elicited rapid bactericidal activity against clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA). The polymer was biocompatible for human cultured ocular and dermal cells. Prophylactic addition of LPEI inhibited the bacterial colonization of human primary dermal fibroblasts (hDFs). In a scratch wound cell migration assay, LPEI attenuated the migration inhibitory effects of bacterial secretions. The polymer neutralized the cytokine release by hDFs exposed to bacterial secretions, possibly by blocking their accessibility to host cell receptors. Topical instillation of LPEI (1 mg/mL) was noncytotoxic and did not affect the re-epithelialization of injured porcine cornea. In a prophylactic in vivo model of S. aureus keratitis, LPEI was superior to gatifloxacin in terms of reducing stimulation of cytokines, corneal edema, and overall severity of the infection. These observations demonstrate therapeutic potential of LPEI for antimicrobial prophylaxis.
AB - Increased evolution of multidrug resistant pathogens necessitates the development of multifunctional antimicrobials. There is a perceived need for developing new antimicrobials that can interfere with acute inflammation after bacterial infections. Here, we investigated the therapeutic potential of linear polyethylenimine (LPEI) in vitro and in vivo. The minimum inhibitory concentration of LPEI ranged from 8 to 32 μg/mL and elicited rapid bactericidal activity against clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA). The polymer was biocompatible for human cultured ocular and dermal cells. Prophylactic addition of LPEI inhibited the bacterial colonization of human primary dermal fibroblasts (hDFs). In a scratch wound cell migration assay, LPEI attenuated the migration inhibitory effects of bacterial secretions. The polymer neutralized the cytokine release by hDFs exposed to bacterial secretions, possibly by blocking their accessibility to host cell receptors. Topical instillation of LPEI (1 mg/mL) was noncytotoxic and did not affect the re-epithelialization of injured porcine cornea. In a prophylactic in vivo model of S. aureus keratitis, LPEI was superior to gatifloxacin in terms of reducing stimulation of cytokines, corneal edema, and overall severity of the infection. These observations demonstrate therapeutic potential of LPEI for antimicrobial prophylaxis.
KW - anti-inflammatory
KW - antimicrobial
KW - linear polyethylenimine
KW - prophylaxis
KW - wound healing
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U2 - 10.1021/acsinfecdis.9b00102
DO - 10.1021/acsinfecdis.9b00102
M3 - Article
C2 - 31099239
AN - SCOPUS:85067065466
SN - 2373-8227
VL - 5
SP - 1411
EP - 1422
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 8
ER -