Fitness trade-offs of multidrug efflux pumps in Escherichia coli K-12 in acid or base, and with aromatic phytochemicals.

Multidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log phase, whereas mdtE expression was upregulated in the transition-to-stationary phase and at pH 5.5 in the log phase. Methyl salicylate did not affect pump gene expression. Our results suggest that lipophilic non-acidic molecules select against a major efflux pump without inducing antibiotic resistance regulons.IMPORTANCEFor drugs that are administered orally, we need to understand how ingested phytochemicals modulate drug resistance in our gut microbiome. Bacteria maintain low-level resistance by proton-motive force (PMF)-driven pumps that efflux many different antibiotics and cell waste products. These pumps play a key role in bacterial defense by conferring resistance to antimicrobial agents at first exposure while providing time for a pathogen to evolve resistance to higher levels of the antibiotic exposed. Nevertheless, efflux pumps confer energetic costs due to gene expression and pump energy expense. The bacterial PMF includes the transmembrane pH difference (ΔpH), which may be depleted by permeant acids and membrane disruptors. Understanding the fitness costs of efflux pumps may enable us to develop resistance breakers, that is, molecules that work together with antibiotics to potentiate their effect. Non-acidic aromatic molecules have the advantage that they avoid the Mar-dependent induction of regulons conferring other forms of drug resistance. We show that different pumps have distinct selection criteria, and we identified non-acidic aromatic molecules as promising candidates for drug resistance breakers.

Descriptive norms caused increases in mask wearing during the COVID-19 pandemic.

Human sociality is governed by two types of social norms: injunctive norms, which prescribe what people ought to do, and descriptive norms, which reflect what people actually do. The process by which these norms emerge and their causal influences on cooperative behavior over time are not well understood. Here, we study these questions through social norms influencing mask wearing during the COVID-19 pandemic. Leveraging 2 years of data from the United States (18 time points; n = 915), we tracked mask wearing and perceived injunctive and descriptive mask wearing norms as the pandemic unfolded. Longitudinal trends suggested that norms and behavior were tightly coupled, changing quickly in response to public health recommendations. In addition, longitudinal modeling revealed that descriptive norms caused future increases in mask wearing across multiple waves of data collection. These cross-lagged causal effects of descriptive norms were large, even after controlling for non-social beliefs and demographic variables. Injunctive norms, by contrast, had less frequent and generally weaker causal effects on future mask wearing. During uncertain times, cooperative behavior is more strongly driven by what others are actually doing, rather than what others think ought to be done.

COVID-19 and friendships: Agreeableness and neuroticism are associated with more concern about COVID-19 and friends' risky behaviors.

Given the importance of friendships during challenging times and the mixed associations between personality traits and disease-related behaviors, we investigated the correlations between personality traits and perceptions of friendships during the COVID-19 pandemic. Data were collected as part of a longitudinal investigation of the correlations between the pandemic and various cooperative relationships. In this investigation, we found that agreeableness and neuroticism predicted participants being more concerned about COVID-19 and bothered by friends' risky behavior, and extraversion predicted enjoying helping friends during the pandemic. Our results suggest that personality differences are associated with how individuals cope with friends' risky behaviors during the COVID-19 pandemic.

Younger people and people with higher subjective SES experienced more negative effects of the pandemic on their friendships.

Friendships provide social support and mental health benefits, yet the COVID-19 pandemic has limited interactions with friends. In August 2020, we asked participants (N = 634) about their friendships during the pandemic as part of a larger study. We found that younger people and people with higher subjective SES reported more negative effects on their friendships, including feeling more isolated and lonelier. We also found that stress, isolation, and guilt were associated with greater COVID-related social risk-taking, such as making and visiting new friends in person. Our results suggest the pandemic is affecting friendships differently across demographic groups and these negative effects might motivate social risk-taking.

Associations Between Change Over Time in Pandemic-Related Stress and Change in Physical Activity.

BACKGROUND: Physical activity (PA) mitigated psychological distress during the initial weeks of the COVID-19 pandemic, yet not much is known about whether PA had effects on stress in subsequent months. We examined the relationship between change over time in COVID-related stress and self-reported change in PA between March and July 2020. METHODS: Latent growth modeling was used to examine trajectories of change in pandemic-related stress and test their association with self-reported changes in PA in an international sample (n = 679). RESULTS: The participants reported a reduction in pandemic-related stress between April and July of 2020. Significant linear (factor mean = -0.22) and quadratic (factor mean = 0.02) changes (Ps < .001) were observed, indicating a deceleration in stress reduction over time. Linear change was related to change in PA such that individuals who became less active during the pandemic reported less stress reduction over time compared with those who maintained or increased their PA during the pandemic. CONCLUSIONS: Individuals who experienced the greatest reduction in stress over time during the pandemic were those who maintained their activity levels or became more active. Our study cannot establish a causal relationship between these variables, but the findings are consistent with other work showing that PA reduces stress.

Using multiple correspondence analysis to identify behaviour patterns associated with overweight and obesity in Vanuatu adults.

OBJECTIVE: The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country. DESIGN: Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed. SETTING: Vanuatu.ParticipantsNi-Vanuatu adults (n 810) aged 20-85 years. RESULTS: Among individuals in the tertile characterized by positive responses to most of or all the twelve modernization questions, weight and measures of body fat and the likelihood that measures of body fat were above the US 75th percentile were significantly greater compared with individuals in the tertiles characterized by mostly or partly negative responses. CONCLUSIONS: The study indicates that MCA can be used to identify individuals or groups at risk for overweight/obesity, based on answers to simply-put questions. MCA therefore may be useful in areas where obtaining detailed information about modernization status is constrained by time, money or manpower.

CYP17 genotype modifies the impact of anthropometric variation on salivary estradiol in healthy women.

Several studies demonstrate that human ovarian function is responsive to the energetic environment, which has led to the development of theoretical models that explain this phenomenon. Although many genes are involved in ovarian hormone production, the possibility that genetic polymorphism may affect ovarian response to energetic conditions has not been considered. Cytochrome P450c17α is an enzyme that produces androgen precursors used to make estrogens during ovarian steroidogenesis, and is encoded by the CYP17 gene. A functionally significant variant within the promoter region of CYP17 has been linked to variation in steroid production, and some evidence suggests that this polymorphism could alter transcription of CYP17 in an insulin-dependent manner. We tested the hypothesis that the CYP17 variant affected the relationship between anthropometric measurements and salivary estradiol in healthy women in the United States (n = 28). PCR-RLFP analysis was used to genotype women for the genetic variant, and estradiol was assayed from saliva by EIA. Moderated regression analysis of these preliminary data revealed a significant interaction between waist-to-hip ratio and CYP17 genotype (P = 0.004). Our study provides evidence that gene-environment interactions should be considered in future adaptive models for human ovarian function. Moreover, our results stand to illuminate possible associations between this genetic variant and reproductive disease.

Modernization and the onset of overweight and obesity in Bougainville and Solomon Islands children: cross-sectional and longitudinal comparisons between 1966 and 1986.

This set of cross-sectional and longitudinal data from children and young adults in certain Bougainville and Solomon Islands populations undergoing rapid modernization during the period 1966-1986 reveals very different responses to essentially the same stimuli-the introduction and widespread availability of western dietary items and reductions in habitual activity. Our analyses of over 2,000 children and young adults first measured in 1966-1972, with follow-up surveys in 1968-1970 and 1985-1986, show changes in overweight/obesity in these communities have their onset around puberty, and are not related to differences in childhood growth stunting. The prevalence of overweight and obesity increased substantially during the period of this study among young adults, particularly women, and in groups with more Polynesian affinities, where the frequency of overweight (BMI ≥ 25) tripled over this 20-year interval. However, the BMI of the more Papuan groups on Bougainville remained remarkably stable, even though they were close to the epicenter of modernization during this period, the Bougainville Copper Mine.