Christina Tobin Kåhrström

Bio: Christina Tobin Kåhrström is an academic researcher. The author has contributed to research in topics: Cellular microbiology & Viral pathogenesis. The author has an hindex of 5, co-authored 124 publications receiving 200 citations.

Entering a post-antibiotic era?

Abstract: Although microbiologists have been ringing the alarm bell for years, the threat of antibiotic resistance recently reached new prominence in the popular press following a declaration by Britain’s chief medical officer, Sally Davies, that the issue should be added to the list of national emergencies. In her speech to members of parliament on the UK Commons Science and Technology Committee, Davies described the issue as an “apocalyptic scenario” and stated that “There are few public health issues of potentially greater importance for society than antibiotic resistance” (The Guardian, 23 Jan 2012). During her address, she noted that about 80% of gonorrhoeal infections are now resistant to antibiotics and that there are around 440,000 new cases of drug-resistant tuberculosis annually. She also added that “we are not using our antibiotics effectively” and told the committee that “We need to get our act together in this country” (International Business Times UK, 24 Jan 2013). The speech comes ahead of the publication of the annual report on infectious diseases, which she said would include “a new cross-government strategy and action plan to tackle this issue” (The Guardian, 23 Jan 2013). The antibiotic resistance problem is not new; however, as Valerie Edwards-Jones from Manchester Metropolitan University explains, “Since 2009, only two new drugs have been released” (The Telegraph, 27 Jan 2013). Margaret Chan, Director-General of the WHO, stated: “In terms of new replacement antibiotics, the pipeline is virtually dry, especially for Gram-negative bacteria.” She warns that we are fast approaching a post-antibiotic era and “an end to modern medicine”, when “Things as common as a strep throat or a child’s scratched knee could once again kill” (International Business Times UK, 24 Jan 2013). Christina Tobin Kåhrström R E S E A R C H H I G H L I G H T S

Environmental microbiology: plant bacteria thrive in storm clouds.

Abstract: The first comprehensive biogeochemical survey of a storm cloud reveals a selection bias for plant-associated bacteria over soil bacteria, which could influence the global distribution of bacteria.

Bacterial pathogenesis: E. coli claims the driving seat for cancer.

Abstract: Inflammation of the gut results in an altered microbiota and enriches for colibactin-producing E. coli , which promotes colorectal cancer.

Antimicrobials: a new drug for resistant bugs.

Abstract: A study reports the discovery of a new antibiotic with a novel mechanism of action and a low propensity to select for resistance.

Bacterial pathogenesis: E. coli claims the driving seat for cancer.

Abstract: Inflammation of the gut results in an altered microbiota and enriches for colibactin-producing E. coli, which promotes colorectal cancer.

Population Genomics of Early Events in the Ecological Differentiation of Bacteria

Abstract: Some Sort of Species Certain populations of bacteria are known to show ecological differentiation, but how this happens has remained controversial. Shapiro et al. (p. 48; see the Perspective by Papke and Gogarten) examined whole-genome sequences from ecologically divergent Vibrio populations and found that genes and genome regions containing so-called “eco-SNPs” (single-nuleotide polymorphisms) have swept through populations. These regions differentiate the bacteria genetically, apparently according to the type of substratum on which they live. Subsequently, tight genotypic clusters may have emerged as a result of preferential recombination occurring within particular habitats. Although specialization into different habitats may reduce gene flow between bacterial populations, the bacteria will always remain open to taking up DNA from other populations and so they cannot be said to be species in the eukaryotic sense. Ecologically separated Vibrio populations diverge by gene-specific rather than genome-wide selective sweeps. Genetic exchange is common among bacteria, but its effect on population diversity during ecological differentiation remains controversial. A fundamental question is whether advantageous mutations lead to selection of clonal genomes or, as in sexual eukaryotes, sweep through populations on their own. Here, we show that in two recently diverged populations of ocean bacteria, ecological differentiation has occurred akin to a sexual mechanism: A few genome regions have swept through subpopulations in a habitat-specific manner, accompanied by gradual separation of gene pools as evidenced by increased habitat specificity of the most recent recombinations. These findings reconcile previous, seemingly contradictory empirical observations of the genetic structure of bacterial populations and point to a more unified process of differentiation in bacteria and sexual eukaryotes than previously thought.

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Abstract: Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as colitis-associated cancers. Genetic polymorphism of innate immune receptors had long been considered a major risk factor for IBD, and the mutations were also recently observed in CRC. Altered microbial composition (termed microbiota dybiosis) and dysfunctional gut barrier manifested by epithelial hyperpermeability and high amount of mucosa-associated bacteria were observed in IBD and CRC patients. The findings suggested that aberrant immune responses to penetrating commensal microbes may play key roles in fueling disease progression. Accumulative evidence demonstrated that mucosa-associated bacteria harbored colitogenic and protumoral properties in experimental models, supporting an active role of bacteria as pathobionts (commensal-derived opportunistic pathogens). Nevertheless, the host factors involved in bacterial dysbiosis and conversion mechanisms from lumen-dwelling commensals to mucosal pathobionts remain unclear. Based on the observation of gut leakiness in patients and the evidence of epithelial hyperpermeability prior to the onset of mucosal histopathology in colitic animals, it was postulated that the epithelial barrier dysfunction associated with mucosal enrichment of specific bacterial strains may predispose the shift to disease-associated microbiota. The speculation of leaky gut as an initiating factor for microbiota dysbiosis that eventually led to pathological consequences was proposed as the “common ground hypothesis”, which will be highlighted in this review. Overall, the understanding of the core interplay between gut microbiota and epithelial barriers at early subclinical phases will shed light to novel therapeutic strategies to manage chronic inflammatory disorders and colitis-associated cancers.

Natural Berberine-Based Chinese Herb Medicine Assembled Nanostructures with Modified Antibacterial Application.

Abstract: The abuse of traditional antibiotics has caused a series of health problems including antimicrobial resistance, which threatens human health. Therefore, searching for broad sources of antimicrobial agents and developing multidimensional strategies to combat bacterial infections are urgent. Here, we reported two natural self-assembling modes between berberine (BBR) and flavonoid glycosides: nanoparticles (NPs) and nanofibers (NFs), which were both mainly governed by electrostatic and hydrophobic interactions. These two nanostructures exhibited different antibacterial properties from BBR. NPs showed significantly enhanced bacteriostatic activity, whereas NFs displayed a much weaker effect than BBR. The distinguishing properties can be attributed to the different spatial configurations and self-assembly processes of NPs and NFs. Flavonoid glycosides and BBR first formed a one-dimensional complex unit and subsequently self-assembled into three-dimensional nanostructures. With the hydrophilic glucuronic acid toward the outside, NPs exhibited stronger affinity to bacteria, thereby inducing the collapse of the bacteria population and the decrease in biofilm. In addition, in vitro hemolysis tests, cytotoxicity tests, and in vivo zebrafish toxicity evaluation showed that the obtained self-assemblies had good biocompatibility. This supramolecular self-assembly strategy can be applied to construct other nanoscale antibacterial drugs and thus provides weapons for the development of self-delivering drugs in bacterial infection treatment.