Background

Our research focuses on an understudied mechanism of antibiotic evasion, called L-form switching. Almost all bacteria are surrounded by a structure called the cell wall, which protects them against environmental stresses and helps with regular division. Many of our most commonly used antibiotics, such as penicillin, target this structure. During treatment with these antibiotics, bacteria usually burst and die, but some can survive in a wall-less state referred to as an L-form, if the surrounding environment provides sufficient osmoprotection. Without the wall, bacteria are fragile and slow growing, but resistant to all types of antibiotics that target this structure. Once antibiotic treatment is concluded, bacteria that survived in an L-form state can rebuild the wall and start dividing rapidly, potentially contributing to recurrent infections.

Importantly, many pathogens, including E. coli and S. aureus, can undergo L-form switching and over the years it has been speculated that the host can provide a supportive environment for the process. L-form switching has been implicated in several recurrent diseases in human and animals, such as sepsis, mastitis, urinary tract and gastrointestinal infections. However, the fragile nature of L-forms and their low numbers in the host's body make them difficult to study and convincing evidence for their role in disease was historically slow to emerge. We use modern molecular methods, advanced fluorescence microscopy and genetic engineering to study the role of L-form switching in bacterial recurrence and antibiotic evasion.

Research

Current Research Project

• Potential role of L-form bacteria in infectious disease recurrence

Teaching

Current Postgraduate Research Supervision

• Jon Chapman
• Stephen Garrett

Publications

• Articles

  • Watson AK, Kepplinger B, Bakhiet SM, Mhmoud NA, Chapman J, Allenby NE, Mickiewicz K, Goodfellow M, Fahal AH, Errington J. Systematic whole-genome sequencing reveals an unexpected diversity among actinomycetoma pathogens and provides insights into their antibacterial susceptibilities. PLoS Neglected Tropical Diseases 2022, 16(7), e0010128.
  • Mickiewicz KM, Kawai Y, Drage L, Gomes MC, Davison F, Pickard R, Hall J, Mostowy S, Aldridge PD, Errington J. Possible role of L-form switching in recurrent urinary tract infection. Nature Communications 2019, 10(1), 4379.
  • Kawai Y, Mercier R, Mickiewicz K, Serafini A, Sorio de Carvalho LP, Errington J. Crucial role for central carbon metabolism in the bacterial L-form switch and killing by β-lactam antibiotics. Nature Microbiology 2019, 4, 1716-1726.
  • Kawai Y, Mickiewicz K, Errington J. Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria. Cell 2018, 172(5), 1038-1049.e10.
  • Mickiewicz KM, Gays F, Lewis RJ, Brooks CG. Mutagenesis of Ly49B Reveals Key Structural Elements Required for Promiscuous Binding to MHC Class I Molecules and New Insights into the Molecular Evolution of Ly49s. Journal of Immunology 2014, 192(4), 1558-1569.
  • Gays F, Koh ASC, Mickiewicz KM, Aust JG, Brooks CG. Comprehensive analysis of transcript start sites in Ly49 genes reveals an unexpected relationship with gene function and a lack of upstream promoters. PLoS ONE 2011, 6(3), e18475.
  • Aust JG, Gays F, Mickiewicz KM, Buchanan E, Brooks CG. The Expression and Function of the NKRP1 Receptor Family in C57BL/6 Mice. Journal of Immunology 2009, 183(1), 106-116.

• Note

  • Mickiewicz KM, Kawai Y, Drage L, Gomes MC, Davison F, Pickard R, Hall J, Mostowy S, Aldridge PD, Errington J. Author Correction: Possible role of L-form switching in recurrent urinary tract infection (Nature Communications, (2019), 10, 1, (4379), 10.1038/s41467-019-12359-3). Nature Communications 2019, 10, 5254.

• Review

  • Errington J, Mickiewicz K, Kawai Y, Wu LJ. L-form bacteria, chronic diseases and the origins of life. Philosophical Transactions of the Royal Society B: Biological Sciences 2016, 371(1707).