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minimal medium supplemented with C12 L-lysine using flow chambers. After killing the antibiotic sensitive population, fresh medium containing colistin and C13
L-lysine was used to label the newly synthesized proteins of persister cells. The
research above concluded that type IV pili and quorum sensing (QS) systems are
important for antibiotic tolerance development in biofilm (Chua et al. 2016). PulsedSILAC approach also has been used to study the proteins that are important for
E. coli persisters reactivation (Spanka et al. 2019).
The persisters formation is associated with reduced metabolic activity (Prax and
Bertram 2014). Starvation induced stringent response have been demonstrated to be
involved in persisters formation (Germain et al. 2013; Kaspy et al. 2013; Khakimova
et al. 2013). Many genes associated with metabolism were found to affect bacterial
persistence (Amato et al. 2014). Besides, metabolomics has also been used to profile the metabolic changes of bacteria challenged with antibiotics (Campos and
Zampieri 2019; Nandakumar et al. 2014; Zampieri et al. 2017). This approach has
been applied to persisters study in the most recent years (Schubert et al. 2015).
Aspartic acid and glutamate have been identified to be critical for S. aureus persisters metabolism by fully 13 C-labeled glucose isotopologue profiling, a well-known
metabolomics approach (Lechner et al. 2014). Proteomics and metabolomics
approaches provide global information to persisters formation mechanism from
protein expression level, which helped us to develop effective strategies to eradicate
persisters during the infection.
5.6 Conclusion
Persisters contribute to the recalcitrance of chronic infections and can thwart the
treatment efforts (LaFleur et al. 2006). More insights into persister cells will inform
better control measures for chronic infections. The understanding about biology of
persisters has made immense progress. Genes involved in persister cells formation
or persistence were identified through transposon mutant library screening, which
will provide more targets for better antibiotics or their leads. In addition, the omics
data of persister cells can reveal more secrets of persisters biology. Metabolomics
could be used to explore the metabolites important for persisters resuscitation.
Those approaches have provided numerous information of persisters physiology for
investigators. A better understanding of persisters formation and their reactivation
mechanisms might facilitate the development of new strategies to eliminate them
(similar to the ‘Shock and Kill’ anti-HIV approach).
5 Molecular and Systems Biology Approaches for Analyzing Drug-Tolerant Bacterial…
minimal medium supplemented with C12 L-lysine using flow chambers. After killing the antibiotic sensitive population, fresh medium containing colistin and C13
L-lysine was used to label the newly synthesized proteins of persister cells. The
research above concluded that type IV pili and quorum sensing (QS) systems are
important for antibiotic tolerance development in biofilm (Chua et al. 2016). PulsedSILAC approach also has been used to study the proteins that are important for
E. coli persisters reactivation (Spanka et al. 2019).
The persisters formation is associated with reduced metabolic activity (Prax and
Bertram 2014). Starvation induced stringent response have been demonstrated to be
involved in persisters formation (Germain et al. 2013; Kaspy et al. 2013; Khakimova
et al. 2013). Many genes associated with metabolism were found to affect bacterial
persistence (Amato et al. 2014). Besides, metabolomics has also been used to profile the metabolic changes of bacteria challenged with antibiotics (Campos and
Zampieri 2019; Nandakumar et al. 2014; Zampieri et al. 2017). This approach has
been applied to persisters study in the most recent years (Schubert et al. 2015).
Aspartic acid and glutamate have been identified to be critical for S. aureus persisters metabolism by fully 13 C-labeled glucose isotopologue profiling, a well-known
metabolomics approach (Lechner et al. 2014). Proteomics and metabolomics
approaches provide global information to persisters formation mechanism from
protein expression level, which helped us to develop effective strategies to eradicate
persisters during the infection.
5.6 Conclusion
Persisters contribute to the recalcitrance of chronic infections and can thwart the
treatment efforts (LaFleur et al. 2006). More insights into persister cells will inform
better control measures for chronic infections. The understanding about biology of
persisters has made immense progress. Genes involved in persister cells formation
or persistence were identified through transposon mutant library screening, which
will provide more targets for better antibiotics or their leads. In addition, the omics
data of persister cells can reveal more secrets of persisters biology. Metabolomics
could be used to explore the metabolites important for persisters resuscitation.
Those approaches have provided numerous information of persisters physiology for
investigators. A better understanding of persisters formation and their reactivation
mechanisms might facilitate the development of new strategies to eliminate them
(similar to the ‘Shock and Kill’ anti-HIV approach).
5 Molecular and Systems Biology Approaches for Analyzing Drug-Tolerant Bacterial…