A Shift to Human Body Temperature (37°C) Rapidly Reprograms Multiple Adaptive Responses in Escherichia coli That Would Facilitate Niche Survival and Colonization.

One of the first environmental cues sensed by a microbe as it enters a human host is an upshift in temperature to 37°C. In this dynamic time point analysis, we demonstrate that this environmental transition rapidly signals a multitude of gene expression changes in Escherichia coli. Bacteria grown at 23°C under aerobic conditions were shifted to 37°C, and mRNA expression was measured at time points after the shift to 37°C (t = 0.5, 1, and 4 h). The first hour is characterized by a transient shift to anaerobic respiration strategies and stress responses, particularly acid resistance, indicating that temperature serves as a sentinel cue to predict and prepare for various niches within the host. The temperature effects on a subset of stress response genes were shown to be mediated by RpoS and directly correlated with RpoS, DsrA, and RprA levels, and increased acid resistance was observed that was dependent on 23°C growth and RpoS. By 4 h, gene expression shifted to aerobic respiration pathways and decreased stress responses, coupled with increases in genes associated with biosynthesis (amino acid and nucleotides), iron uptake, and host defense. ompT, a gene that confers resistance to antimicrobial peptides, was highly thermoregulated, with a pattern conserved in enteropathogenic and uropathogenic E. coli strains. An immediate decrease in curli gene expression concomitant with an increase in flagellar gene expression implicates temperature in this developmental decision. Together, our studies demonstrate that temperature signals a reprogramming of gene expression immediately upon an upshift that may predict, prepare, and benefit the survival of the bacterium within the host. IMPORTANCE As one of the first cues sensed by the microbe upon entry into a human host, understanding how bacteria like E. coli modulate gene expression in response to temperature improves our understanding of how bacteria immediately initiate responses beneficial for survival and colonization. For pathogens, understanding the various pathways of thermal regulation could yield valuable targets for anti-infective chemotherapeutic drugs or disinfection measures. In addition, our data provide a dynamic examination of the RpoS stress response, providing genome-wide support for how temperature impacts RpoS through changes in RpoS stability and modulation by small regulatory RNAs.

The Presence of Diabetes and Higher HbA1c Are Independently Associated With Adverse Outcomes After Surgery.

OBJECTIVE: Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA1c as a continuous measure, with postoperative outcomes. RESEARCH DESIGN AND METHODS: In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA1c <5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model. RESULTS: Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05-1.58]; P = 0.014), major complications (1.32 [1.14-1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28-1.75]; P < 0.001), mechanical ventilation (1.67 [1.32-2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04-1.12]; P < 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01-1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07-1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03-1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors. CONCLUSIONS: Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery.