Student information and resources (http://www.hakanssonlab.com/lab/studentres.asp)

Below, please find information and selected references that will describe the background to the projects we are conducting in the laboratory. Some references are papers produced by the lab and others are review articles meant to inform you about the field. I have tried to annotate the references based on how important they are and advice you to read the "recommended" references first. If you are interested in some aspects of these projects please contact me by e-mail: anders_p.hakansson@med.lu.se

Pneumococcal pathogenesis

We are interested in better understanding how the gram-positive, extracellular pathogen Streptococcus pneumoniae (pneumococcus) interact with the host mucosa in the respiratory tract. We have reently shown that pneumococci colonize the nasopharynx as a biofilm and have characterized the factors required for optimal colonization and biofilm formation and how these factors promote optimal genetic exchange by this naturally ompetent organism. We have also recently identified some factors involved in the mechanisms behinds transition from pneumococcal colonization to infection. Our studies are focused on bacterial factors that are promote colonization and infection of the human host but also on the strategies used by the host to protect itself from bacterial challenge, how the host and bacteria communicate and how the nasopharyngeal microbiome modulates the signals transduced.

Background info    
Wikipedia Click here to see general information about Streptococcus pneumoniae. Link
Kadioglu et al. 2008 Review article presenting the basic concepts and molecules involved in pneumococcal pathogenesis. (Recommended overview.) PDF

Jedrzejas, 2001 Review article (a little older and not as up to date) about pneumococcal pathogenesis. More of a listing of pneumococcal virulence factors but will provide additional information to the Kadioglu paper. (Recommended additional reading.) PDF
McCullers, 2014 Review article on influenza virus and pneumococcal superinfection (recommended) PDF
Bogaert, 2011 Paper on the role of the nasopharyngeal microbiome on colonization and disease in children (recommended) PDF
Hammerschmid, 2006 Review article expanding on the adherence mechanisms of pneumococci. (Optional reading) PDF
Higgins, 2001 Review article about the structure and function of ABC transporters. (Optional background reading) PDF
Our publications    
Smith, 2002 Paper describing the phenotypes of DLDH-mutant pneumococci. (Mol. Microbiol; Recommended reading) PDF
Hakansson, 2007 Paper characterizing the enzymeatica activity of pneumococcal DLDH. (JBC; Optional reading.) PDF
Tyx, 2011 DLDH regulates raffinose transport in Streptococcus pneumoniae. (Infect. Immun; Optional reading.) PDF
Marks, 2012 Streptococcus pneumoniae forms biofilms during colonization of mice that are phenotypically reproduced using epithelial substrata in vitro. (Infect Immun.; Recommended reading) PDF
Marks, 2012 High levels of genetic recombination during nasopharyngeal carriage and biofilm formation in Streptococcus pneumoniae (MBio; Recommended reading) PDF
Marks, 2013 Interkingdom signalling innvolved in transition from colonization to infection (MBio; recommended) PDF
Marks, 2014 Survival of biofilm bacteria on fomites (Infect. Immun; optional) PDF
Marks, 2014 Group A streptococcal natural transformation during biofilm growth (JID; optional) PDF
Pettigrew, 2014 Transcriptional analysis of biofilm and dispersed, virulent populations of pneumococci (Infect. Immun, recommended) PDF

Bactericidal activity of the human milk protein-lipid complex HAMLET

Breast-feeding is well documented to protect against a variety of infections, including strong protection against respiratory tract infections. During my graduate studies I discovered a protein fraction from human milk, HAMLET that induced apoptosis in tumor cells without affecting healthy cells. Besides killing tumor cells, HAMLET effectively kills pneumococci as well as other respiratory tract pathogens by inducing an apoptosis-like death that requires a sodium-dependent calcium influx and kinase activity. We have also learned that, using the same mechanism, HAMLET can synergize with common antibiotics to make antibiotic-resistant bacteria sensitive to the antibiotics they are resistant to. Our current projects are aimed at understanding the mechanism of HAMLET-induced bacterial death as well as bacterial death from physiological stressors, and the potential use of HAMLET in preventing and treating established pneumococcal infections. Understanding these mechanisms may also help us understand how HAMLET kills tumor cells.

Background info    
Rice, 2008 Review of programmed cell death in bacteria. (Recommended reading.) PDF
Lewis, 2000 Review of programmed cell death in bacteria. Older but more encompassing. (Recommended additioanl reading) PDF
Engelberg-Kulka, 2006 Review of programmed cell death in bacteria. More focused on toxin-anti-toxin systems. (Optional reading.) PDF
Our publications    
Hakansson, 1999 My thesis descibing the anti-tumor activity of HAMLET and the background to the bacterial project. (Comprehensive additional reading) PDF
Hakansson, 1995 Original description of HAMLET (MAL) and its anti-tumor effect. (PNAS; Optional reading.) PDF
Svensson, 2000 Paper describing the structural conformation of HAMLET. (PNAS; Optional reading.) PDF
Hakansson, 2000 Paper describing HAMLET structure and its anti-bacterial activity. (Mol Microbiol; Recommended reading.) PDF
Hakansson, 2011 HAMLET induced apoptotis-like death in Streptococcus pneumoniae. (PLoS One; Recommended reading.) PDF
Permyakov, 2011 A novel prepapration of HAMLET-like complexes (Biochimie; Optional reading.) PDF
Permyakov, 2012 Oleic acid is a key cytotoxic component of HAMLET-like complexes (Biol. Chem; Optional reading.) PDF
Clementi, 2012 A novel death pathway induced in Streptococcus pneumoniae by a human milk protien-lipid complex, HAMLET (JBC; Recommended reading.) PDF
Marks, 2012 HAMLET sensitizes bacteria to traditional antimicrobial agents (PLoS One; Recommended reading.) PDF
Clementi, 2013 Equine lysozyme coupled with oleic acid kills pneumococci in a similar way to HAMLET (PLoS One; Recommended reading.) PDF
Marks, 2013 HAMLET sensitizes MRSA to methicillin and other antibiotics (PLoS One; Recommended reading.) PDF
Clementi, 2014 Methodology to measure cell death and ion transport in bacteria (J Vis Exp; Optional reading.) PDF