Studying Bacterial Persistence: Established Methods and Current Advances

Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes

“…Phenotypic antimicrobial tolerance by persistence was originally identified and defined as the ability of a small fraction of an isogenic bacterial population to escape the antimicrobial activity of a particular agent in the absence of any increase in the agent’s minimum inhibitory concentration for this population ( 33 – 35 ). Antimicrobial-tolerant persistent bacteria display an increase in the minimum time needed to kill 99.99% of the population (MDK 99.99 ) as well as heterogeneity in cellular susceptibility in a culture ( 26 , 27 , 29 , 36 – 38 ). These changes, relevant only to bactericidal antibiotics, result in a biphasic mortality curve ( 26 , 27 , 36 – 39 ).…”

“…Antimicrobial-tolerant persistent bacteria display an increase in the minimum time needed to kill 99.99% of the population (MDK 99.99 ) as well as heterogeneity in cellular susceptibility in a culture ( 26 , 27 , 29 , 36 – 38 ). These changes, relevant only to bactericidal antibiotics, result in a biphasic mortality curve ( 26 , 27 , 36 – 39 ). This phenomenon has traditionally been called persistence, and bacteria displaying this phenotype, persisters ( 26 , 27 , 29 , 36 , 37 ).…”

“…These changes, relevant only to bactericidal antibiotics, result in a biphasic mortality curve ( 26 , 27 , 36 – 39 ). This phenomenon has traditionally been called persistence, and bacteria displaying this phenotype, persisters ( 26 , 27 , 29 , 36 , 37 ). The term “antimicrobial tolerance/persistence” is used here to describe the small fraction of single cell heterogeneous antimicrobial-tolerant persister cells ( 37 , 38 , 40 ).…”

Potential Therapeutic Targets for Combination Antibody Therapy against Pseudomonas aeruginosa Infections

“…Hence, this class has several very promising targets for antibody therapy development. Additionally, they do not impose “life-or-death” selective pressure, allowing therapeutic efficacy to be preserved beyond what is common for many antibiotics, which experience emergence of resistance within a short time of their entrance to the market [ 31 , 37 ]. Several common members of the toxin/invasin class, which are (1) ubiquitously and extracellularly expressed or secreted, (2) key mediators of virulence and pathogenicity, (3) responsive to antibodies, and (4) specific to P. aeruginosa , are discussed below and should be strongly considered as a part of any therapeutic antibody strategy.…”

“…According to this hypothesis, as borne out by numerous studies, persistence may be a transient state, which may or may not be passed to subsequent generations based on the underlying mechanism of action. Alternatively, several genes have been identified (e.g., hip-high persistence [ 27 ] and GlpD—sn-glycerol-3-phosphate dehydrogenase [ 28 ]) and have been suggested to confer phenotypic persistence, a characteristic which may prove heritable [ 29 , 30 , 31 ]. The persister cell’s phenotypic switch, which is likely the result of complex signaling cascade(s), between metabolically quiescent and metabolically active may prove to be an incredibly important drug target; however, an in-depth discussion of the variability and complexity is beyond the scope of the current paper and the reader is referred to several good recent reviews of the topic, specifically that from Kaldalu et al, in 2020 [ 32 ] and Louwagie et al, in 2021 [ 30 ].…”