Search

The rise of multidrug-resistant bacteria is a global concern, leading to a renewed reliance on older antibiotics like polymyxins as a last resort. Polymyxins, cationic cyclic peptides synthesized nonribosomally, feature a hydrophobic acyl tail and positively charged residues. Their antimicrobial mechanism involves initial interaction with Gram-negative bacterial outer-membrane components through polar and hydrophobic interactions. Outer membrane vesicles (OMVs), nano-sized proteoliposomes secreted from the outer membrane of Gram-negative bacteria, play a crucial role in tolerating harmful molecules, including cationic peptides such as polymyxins. Existing literature has documented environmental changes’ impact on modulating OMV properties in Salmonella Typhimurium. However, less information exists regarding OMV production and characteristics in Salmonella Typhi. A previous study in our laboratory showed that S. Typhi ΔmrcB, a mutant associated with penicillin-binding protein (PBP, a β-lactam antibiotic target), exhibited hypervesiculation. Consequently, this study investigated the potential impact of β-lactam antibiotics on promoting polymyxin tolerance via OMVs in S. Typhi. Our results demonstrated that sub-lethal doses of β-lactams increased bacterial survival against polymyxin B in S. Typhi. This phenomenon stems from β-lactam antibiotics inducing hypervesiculation of OMVs with higher affinity for polymyxin B, capturing and diminishing its biologically effective concentration. These findings suggest that β-lactam antibiotic use may inadvertently contribute to decreased polymyxin effectivity against S. Typhi or other Gram-negative bacteria, complicating the effective treatment of infections caused by these pathogens. This study emphasizes the importance of evaluating the influence of β-lactam antibiotics on the interaction between OMVs and other antimicrobial agents.

Growing rates of childhood obesity globally create concern for individuals’ health outcomes and demands on health systems. While many policy approaches focus on macro-level interventions, we examine how the type of stability of a family structure might provide opportunities for policy interventions at the micro level. We examine the association between family structure trajectories and childhood overweight and obesity across three Anglophone countries using an expanded set of eight family structure categories that capture biological relationships and instability, along with potential explanatory variables that might vary across family trajectories and provide opportunities for intervention, including access to resources, family stressors, family structure selectivity factors, and obesogenic correlates. We use three datasets that are representative of children born around the year 2000 and aged 11 years old in Australia (n = 3329), the United Kingdom (n = 11,542), and the United States (n = 8837) and nested multivariate multinomial logistic regression models. Our analyses find stronger relationships between child overweight and obesity and family structure trajectories than between child obesity and obesogenic factors. Children in all three countries are sensitive to living with cohabiting parents, although in Australia, this is limited to children whose parents have been cohabiting since before their birth. In the UK and US, parents starting their cohabitation after the child’s birth are more likely to have children who experience obesity. Despite a few differences across cross-cultural contexts, most of the relationship between family structures and child overweight or obesity is connected to differences in families’ access to resources and by the types of parents who enter into these family structures. These findings suggest policy interventions at the family level that focus on potential parents’ education and career prospects and on income support rather than interventions like marriage incentives.