Sotolon is a natural virulence mitigating agent in Serratia marcescens

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ORIGINAL PAPER

Sotolon is a natural virulence mitigating agent in Serratia marcescens Hisham A. Abbas1   · Reham M. Goda2 Received: 31 March 2020 / Revised: 25 August 2020 / Accepted: 12 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Serratia marcescens is an emerging opportunistic bacterium that can cause healthcare-associated infections. The high rate of multidrug resistance and the ability to produce a set of virulence factors, by which it can produce infectious diseases makes it urgent to find an alternative approach to the treatment of such infections. Disarming of virulence by targeting of quorum sensing (QS) as the regulating mechanism of virulence is a promising approach that has no effect on bacterial growth that is considered a key factor in emergence of resistance. This study was designed to investigate the ability of sub-inhibitory concentrations (sub-MICs) of sotolon to attenuate virulence of a clinical isolate of S. marcescens. Sotolon at 25 and 50 μg/ ml inhibited 35.2 and 47.5% of biofilm formation, respectively. The inhibition of swimming motility were 41.4 and 69.3%, while that of swarming motility were 77.6 and 86.8% at 25 and 50 µg/ml, respectively. Moreover, sotolon reduced prodigiosin production by 76.6 and 87.6% at concentrations of 25 and 50 µg/ml, respectively. Protease activity was reduced by 25 µg/ml of sotolon by 54.8% and was completely blocked at 50 µg/ml. The relative expression of genes regulating virulence factors decreased by 40% for fimA, 29% for fimC, 59% for flhC, 57% for flhD, 39% for bsmB, 37% for rssB, 49% for rsmA, 54% for pigP, and 62% for shlA gene in the presence of 50 µg/ml sotolon. In conclusion, sotolon is an anti-virulence agent that could be used for the treatment of S.marcescens hospital-acquired infections. Keywords  Serratia marcescens · Antibiotic resistance · Anti-virulence · Sotolon

Introduction Serratia marcescens is a facultative anaerobic motile Gramnegative bacillus that belongs to the family Enterobacteriaceae. It is of great importance due to the fact of being an opportunistic human pathogen that can cause a variety of healthcare-associated infections (Kida et al. 2007). The infections include central line associated blood stream infections, pneumonia, endocarditis, urinary tract infections and osteomyelitis (Van Houdt et al. 2007; Redondo-Bravo et al. 2019). Moreover, it is considered a food-borne pathogen because of its ability to colonize the gastrointestinal tract (Cristina et al. 2019). Furthermore, the common multidrug Communicated by Erko stackebrandt. * Hisham A. Abbas [email protected] 1



Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt



Department of Microbiology and Biotechnology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Mansoura, Egypt

2

resistance nature of S. marcescens complicates the treatment of its infections (González-Juarbe et al. 2015). Many virulence factors contribute to the ability of S. marces