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Secnidazole Is a Promising Imidazole Mitigator of Serratia marcescens Virulence

Ahdab N Khayyat¹, Hisham A Abbas², Maan T Khayat¹

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

|November 27, 2021

Abstract:

Serratia marcescens is an opportunistic pathogen that causes diverse nosocomial infections. S. marcescens has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in S. marcescens by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of S. marcescens. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole's protective activity against S. marcescens pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the S. marcescens SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced S. marcescens virulence factor production in vitro and diminished its pathogenesis in mice. The insilico docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by S. marcescens.

Insights

Secnidazole effectively reduces virulence factors and pathogenesis in *Serratia marcescens* infections. This study shows secnidazole

Area of Science:

Microbiology
Infectious Diseases
Pharmacology

Background:

*Serratia marcescens* is a significant opportunistic pathogen causing nosocomial infections.
This bacterium exhibits antibiotic resistance and possesses numerous virulence factors.
Quorum sensing (QS) regulates virulence factors in *S. marcescens*, presenting a therapeutic target.

Purpose of the Study:

To evaluate the anti-virulence potential of secnidazole against a clinical isolate of *S. marcescens*.
To investigate the impact of secnidazole on *S. marcescens* virulence factors and pathogenesis.
To explore the molecular mechanism of secnidazole's action on the SmaR QS receptor.

Main Methods:

In vitro assessment of secnidazole's effects on virulence factors (proteases, hemolysin, prodigiosin) and biofilm formation at sub-inhibitory concentrations (sub-MICs).
In vivo evaluation of secnidazole's protective efficacy against *S. marcescens* pathogenesis in a mouse model.
In silico molecular docking to analyze secnidazole's binding affinity to the SmaR QS receptor.

Main Results:

Secnidazole significantly reduced the production of virulence factors and swarming motility in *S. marcescens* in vitro.
Sub-MICs of secnidazole diminished *S. marcescens* pathogenesis in a murine infection model.
Molecular docking indicated that secnidazole effectively binds to the SmaR QS receptor, potentially inhibiting autoinducer binding.

Conclusions:

Secnidazole demonstrates significant anti-virulence properties against *Serratia marcescens*.
The drug acts by interfering with quorum sensing signaling pathways.
Secnidazole is a promising therapeutic agent for controlling *S. marcescens* infections, potentially overcoming antibiotic resistance.

Read full analysis

Keywords:

Serratia marcescens anti-quorum sensing agents anti-virulence agents pathogenesis quorum sensing secnidazole virulence factors

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