Bacterial Histidine Kinase and the Development of Its Inhibitors in the 21st Century
Ragib Ahsan,
Sumaiya Kifayat,
Krishan Kumar Pooniya,
Sunita Kularia,
Bhavani Sailu Adimalla,
Bharat Kumar Reddy Sanapalli,
Vidyasrilekha Sanapalli,
Dilep Kumar Sigalapalli
Affiliations
Ragib Ahsan
Department of Pharmacy, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India
Sumaiya Kifayat
Department of Pharmacy, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India
Krishan Kumar Pooniya
Department of Pharmacy, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India
Sunita Kularia
Department of Pharmacology, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India
Bhavani Sailu Adimalla
Department of Pharmaceutical Analysis, Vignan Pharmacy College, Jawaharlal Nehru Technological University, Vadlamudi, Guntur 522213, Andhra Pradesh, India
Bharat Kumar Reddy Sanapalli
Department of Pharmacology, School of Pharmacy & Technology Management, SVKM’s Narsee Monjee Institute of Management Studies (NMIMS) Deemed to-be-University, Jadcherla 509301, Hyderabad, India
Vidyasrilekha Sanapalli
Department of Pharmaceutical Chemistry, School of Pharmacy & Technology Management, SVKM’s Narsee Monjee Institute of Management Studies (NMIMS) Deemed to-be-University, Jadcherla 509301, Hyderabad, India
Dilep Kumar Sigalapalli
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
Bacterial histidine kinase (BHK) is a constituent of the two-component signaling (TCS) pathway, which is responsible for the regulation of a number of processes connected to bacterial pathogenicity, virulence, biofilm development, antibiotic resistance, and bacterial persistence. As BHK regulation is diverse, inhibitors can be developed, such as antibiotic synergists, bacteriostatic/bactericidal agents, virulence inhibitors, and biofilm inhibitors. Inhibition of essential BHK has always been an amenable strategy due to the conserved binding sites of the domains across bacterial species and growth dependence. Hence, an inhibitor of BHK might block multiple TCS regulatory networks. This review describes the TCS system and the role of BHK in bacterial virulence and discusses the available inhibitors of BHK, which is a specific response regulator with essential structural features.
