Nair, A. R. | Search bioRxiv

bioRxiv2025

Simple Sequence Repeats Mediate Phase Variation of the Mucoid Phenotype in Hypervirulent Klebsiella pneumoniae

Hypervirulent Klebsiella pneumoniae (HVKp) express a thick mucoid capsular polysaccharide which is essential for virulence and survival in the bloodstream but inhibits epithelial adhesion and invasion. The molecular mechanisms regulating capsule expression to rapidly adapt to these distinct niches are unknown. Here, we show that high frequency mutations in a poly-G repeat in the regulator of mucoid phenotype gene, rmpA, mediates reversible ON/OFF phase variation of the mucoid phenotype. We find that these mutations generate subpopulations of bacteria with reduced capsule expression and mucoidy. In vitro and in vivo infection models reveal that phase variation to the OFF state facilitates epithelial cell infection while ON switching enhances resistance to the bactericidal activity of human serum and systemic spread to the liver and spleen in a murine infection model. Genomic analysis reveals that the phase variation mechanism is a conserved feature of all HVKp and that additional novel DNA repeats in rmpD and rmpC drive different combinations of capsule mucoidy and hyperexpression phenotypes. These findings establish a mechanistic basis for how HVKp occupy such a diverse array of niches during infection, with important implications for the design and implementation of Kp-specific vaccines and therapies.

microbiology↗

bioRxiv2022

Social Curiosity in Monkeys

Humans and nonhuman animals derive value from many different sources. Some of these sources, notably primary reinforcers like food, are clearly rewarding and can powerfully shape our behaviors. Other sources of reward, such as information, are more intangible and abstract. Like humans, nonhuman primates also find information inherently rewarding, displaying a preference to reveal information about upcoming primary reinforcers even though the information has no bearing on the outcome itself. For animals living in social groups, the need for information extends beyond primary reinforcers like food. They need to acquire information from others or about others. This is especially true for animals, such as nonhuman primates, which live in large and often hierarchically organized societies, where processing social information for the purpose of learning and socializing can be just as critical to survival. To quantify curiosity for knowing social information in monkeys, we extend the advanced informationseeking paradigm (Bromberg-Martin and Hikosaka, 2009) into the realm of abstract, social information. We first replicated the finding that monkeys prefer advanced information about juice size (Bromberg-Martin and Hikosaka, 2009). We next trained monkeys on a social variant of this task. In the advanced social information-seeking task, monkeys had the option to choose a cue that tells them in advance the valence, or facial expression, on a monkeys face that they will be viewing before receiving the invariant amount of juice. Even though this cue did not impact which facial expression the monkeys would see, they preferred to know the valence of the facial expression in advance. Our results indicate that information-seeking behavior generalizes to seeking social information. Our findings also suggest that curiosity in nonhuman primates can be translated into increasingly abstract levels of information.

animal behavior and cognition↗