Bacterial behavior in human blood reveals complement evaders with some persister-like features

Abstract

Bacterial bloodstream infections (BSI) are a major health concern and can cause up to 40% mortality. Pseudomonas aeruginosa BSI is often of nosocomial origin and is associated with a particularly poor prognosis. The mechanism of bacterial persistence in blood is still largely unknown. Here, we analyzed the behavior of a cohort of clinical and laboratory Pseudomonas aeruginosa strains in human blood. In this specific environment, complement was the main defensive mechanism, acting either by direct bacterial lysis or by opsonophagocytosis, which required recognition by immune cells. We found highly variable survival rates for different strains in blood, whatever their origin, serotype, or the nature of their secreted toxins (ExoS, ExoU or ExlA) and despite their detection by immune cells. We identified and characterized a complement-tolerant subpopulation of bacterial cells that we named “evaders”. Evaders shared some features with bacterial persisters, which tolerate antibiotic treatment. Notably, in bi-phasic killing curves, the evaders represented 0.1–0.001% of the initial bacterial load and displayed transient tolerance. However, the evaders are not dormant and require active metabolism to persist in blood. We detected the evaders for five other major human pathogens: Acinetobacter baumannii, Burkholderia multivorans, enteroaggregative Escherichia coli, Klebsiella pneumoniae, and Yersinia enterocolitica. Thus, the evaders could allow the pathogen to persist within the bloodstream, and may be the cause of fatal bacteremia or dissemination, in particular in the absence of effective antibiotic treatments.

Oregano Oil and Harmless Blue Light to Synergistically Inactivate Multidrug-Resistant Pseudomonas aeruginosa

“…Open wound infections of Pa can lead to bacterial bloodstream infections, bacteremia, and septicemia ( Pont et al, 2020 ), in association with a high death rate. Should the infection not be kept under check in a timely fashion, the fatality rate can be as high as 45% ( Aydın et al, 2018 ).…”

Serum C1q Levels Have Prognostic Value for Sepsis and are Related to the Severity of Sepsis and Organ Damage

“…C1q can combine with bacterial lipopolysaccharide components to activate the complement system, in the case of immune dysfunction, the complement system causes a large consumption of C1q in order to resist inflammatory damage, and finally leads to the reduction of its level. 25 Studies suggest that the classical activation pathway of complement induced by fungi plays only a minor role in the mixed infection of multiple pathogens, but if it is a simple fungal infection, such as Candida albicans , the classical activation pathway of fungi by combining with yeast and mycelium cannot be ignored. 26 Viral infection also causes a similar depletion effect on complement components of classical activation pathways.…”

Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation

“…Changes in the abundance of MBIassociated enteric strains can precede BSI episodes in patients undergoing HCT (16,19,26). In addition to MBI, different bacterial strains of the same species can respond differently to selective pressures (27), with certain strains being more fit than other closely related ones (28,29). Being able to identify and subsequently analyze strain variation (30) could help define how BSIs occur in patients.…”