Chlorhexidine (CHX) has been used to control dental caries caused by acid-tolerant bacteria such as Streptococcus mutans since the 1970s. Repeat CHX exposure for other bacterial species results in the development of variants with reduced susceptibility that also become more resistant to other antimicrobials. It has not been tested if such variants arise when streptococci are exposed to CHX. Here, we passaged S. mutans in increasing concentrations of CHX and isolated spontaneously arising reduced susceptibility variants (RSVs) from separate lineages that have MICs that are up to 3-fold greater than the parental strain. The RSVs have increased growth rates at neutral pH and under acidic conditions in the presence of CHX but accumulate less biomass in biofilms. RSVs display higher MICs for daptomycin and clindamycin but increased sensitivity to dental-relevant antimicrobials triclosan and sodium fluoride. Plate-based assays for competition with health-associated oral streptococci revealed decreased bacteriocin production by the RSVs, increased sensitivity to hydrogen peroxide, and diminished competitive fitness in a human-derived ex vivo biofilm consortium. Whole-genome sequencing identified common single nucleotide polymorphisms (SNPs) within a diacylglycerol kinase homolog and a glycolipid synthesis enzyme, which could alter the accumulation of lipoteichoic acids and other envelope constituents, as well as a variety of mutations in other genes. Collectively, these findings confirm that S. mutans and likely other streptococci can develop tolerance to CHX but that increased tolerance comes at a fitness cost, such that CHX-induced variants that spontaneously arise in the human oral cavity may not persist.

Nearly all scholarship on radical political movements suggests that participation in formal politics will lead to moderation. Yet Iraq's Sadrist Movement, the Shi'a Islamist group headed by Muqtada al-Sadr, defies the widespread assumption that political inclusion leads to moderation by giving a group a greater stake in the system. This paper will examine the Sadrist Movement to explore the impact of unstable security conditions on the calculations and actions of political movements. In late 2004, the Sadrist Movement recognized the legitimacy of the Iraqi state, ceased using violence and entered electoral politics. The literature suggests that the Sadrist Movement should have continued to moderate in response to further political and material incentives. However, in 2006 the Sadrists returned to violence and grew increasingly hostile toward democratic politics. Why did the Sadrist Movement reverse course in this manner? This work argues that unstable environments, such as that of post-2003 Iraq, can cause parties to reject the incentives of inclusion within the state political system.