Pathogenicity of clinical Salmonella enterica serovar Typhimurium isolates from Thailand in a mouse colitis model

Salmonella enterica serovar Typhimurium (S. Typhimurium [STM]) is a leading cause of nontyphoidal salmonellosis (NTS) worldwide. The pathogenesis of NTS has been studied extensively using a streptomycin-pretreated mouse colitis model with the limited numbers of laboratory STM strains. However, the pathogenicity of the clinically isolated STM (STMC) strains endemic in Thailand in mice has not been explored. The aim of this study was to compare the pathogenicity of STMC strains collected from Northern Thailand with the laboratory STM (IR715) in mice. Five STMC isolates were obtained from the stool cultures of patients with acute NTS admitted to Maharaj Nakorn Chiang Mai Hospital in 2016 and 2017. Detection of virulence genes and sequence type (ST) of the strains was performed. Female C57BL/6 mice were pretreated with streptomycin sulfate 1 day prior to oral infection with STM. On Day 4 postinfection, mice were euthanized, and tissues were collected to analyze the bacterial numbers, tissue inflammation, and cecal histopathological score. We found that all five STMC strains are ST34 and conferred the same or reduced pathogenicity compared with that of IR715 in mice. A strain-specific effect of ST34 on mouse gut colonization was also observed. Thailand STM ST34 exhibited a significant attenuated systemic infection in mice possibly due to the lack of spvABC-containing virulence plasmid.     

On the relevance of precision autophagy flux control in vivo – Points of departure for clinical translation

ABSTRACT

Macroautophagy (which we will call autophagy hereafter) is a critical intracellular bulk degradation system that is active at basal rates in eukaryotic cells. This process is embedded in the homeostasis of nutrient availability and cellular metabolic demands, degrading primarily long-lived proteins and specific organelles.. Autophagy is perturbed in many pathologies, and its manipulation to enhance or inhibit this pathway therapeutically has received considerable attention. Although better probes are being developed for a more precise readout of autophagic activity in vitro and increasingly in vivo, many questions remain. These center in particular around the accurate measurement of autophagic flux and its translation from the in vitro to the in vivo environment as well as its clinical application. In this review, we highlight key aspects that appear to contribute to stumbling blocks on the road toward clinical translation and discuss points of departure for reaching some of the desired goals. We discuss techniques that are well aligned with achieving desirable spatiotemporal resolution to gather data on autophagic flux in a multi-scale fashion, to better apply the existing tools that are based on single-cell analysis and to use them in the living organism. We assess how current techniques may be used for the establishment of autophagic flux standards or reference points and consider strategies for a conceptual approach on titrating autophagy inducers based on their effect on autophagic flux . Finally, we discuss potential solutions for inherent controls for autophagy analysis, so as to better discern systemic and tissue-specific autophagic flux in future clinical applications.

Abbreviations: GFP: Green fluorescent protein; J: Flux; MAP1LC3/LC3: Microtubule-associated protein 1 light chain 3; n_A: Number of autophagosomes; TEM: Transmission electron microscopy; τ: Transition time     

Changes in population sizes and distribution of fur seals at Marion Island

 Population censuses of the Antarctic fur seal (Arctocephalus gazella) and the sub-Antarctic fur seal (A. tropicalis) were conducted during the 1994/1995 breeding season at Marion Island. Pup numbers, determined from direct counts and a mark-recapture experiment, were used to estimate population sizes. Pup numbers of A. tropicalis showed a mean annual change of 2.0% over the previous 6 years, culminating in an estimated total population of 49, 523 for 1994/1995. The population appears to be entering the maturity phase of population growth and may therefore have recovered from the effects of uncontrolled sealing that ended in the early twentieth century. Numbers at the major colonies on Marion Island showed little change since 1989 and these sites may have reached carrying capacity. The extension of breeding to other parts of the island continues. Over the same period, A. gazella pup numbers showed a mean annual change of 17% and the total population numbered 1,205 in 1994/1995. This species has possibly entered the rapid recolonisation phase of population growth. A few hybrid seals were found. Received: 25 October 1995/Accepted: 14 April 1996