Proteus mirabilisemploys a contact-dependent killing system against competingEnterobacteriaceae

Many bacterial species encode systems for interference competition with other microorganisms. Some systems are effective without contact (e.g. through secretion of toxins), while other systems (e.g. Type VI secretion system (T6SS)) require direct contact between cells. Here, we provide the initial characterization of a novel contact-dependent competition system forProteus mirabilis. In neonatal mice, a commensalP. mirabilisstrain apparently eliminated commensalEscherichia coli. We replicated the phenotypein vitroand showed thatP. mirabilisefficiently reduced viability of severalEnterobacteriaceaespecies, but not Gram-positive species or yeast cells. Importantly,P. mirabilisstrains isolated from humans also killedE. coli. Reduction of viability occurred from early stationary phase to 24h of culture and was observed in shaking liquid media as well as on solid media. Killing required contact, but was independent of T6SS, the only contact-dependent killing system described forP. mirabilis. Expression of the killing system was regulated by osmolarity and components secreted into the supernatant. Stationary phaseP. mirabilisculture supernatant itself did not kill but was sufficient to induce killing in an exponentially growing co-culture. In contrast, killing was largely prevented in media with low osmolarity. In summary, we provide the initial characterization of a potentially novel interbacterial competition system encoded inP. mirabilis.IMPORTANCEThe study of bacterial competition systems has received significant attention in recent years. These systems collectively shape the composition of complex ecosystems like the mammalian gut. They are also being explored as narrow-spectrum alternatives to specifically eliminate problematic pathogenic species. However, many competition systems that effectively workin vitrodo not show strong phenotypes in the gut. Our study was informed by an observation in infant mice. Furtherin vitrostudies confirmed thatP. mirabiliswas able to kill severalEnterobacteriaceaespecies. This killing system is novel forP. mirabilisand might represent a new function of a known system or even a novel system, as the observed characteristics do not fit with described contact-dependent competition systems. Competition systems are frequently present in multipleEnterobacteriaceaespecies. If present or transferred into a probiotic, it might be used in the future to reduce blooms of pathogenicEnterobacteriaceaeassociated with disease.