Efficient microbial colony growth dynamics quantification with ColTapp, an automated image analysis application

Bär, Julian; Boumasmoud, Mathilde; Kouyos, Roger D.; Vulin, Clément

doi:10.1038/s41598-020-72979-4

Cited by 46 publications

(58 citation statements)

References 49 publications

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“…Automated Agar-Plate Imaging and Single-Cell Time-Lapse Microscopy. To determine colony growth dynamics, bacteria were plated onto agar plates, incubated at 37°C, and imaged every 10 min for 48 h. Analysis of colony growth kinetics was performed with our in-house software "ColTapp" (6,58). Bacterial single-cell lag times were quantified by time-lapse microscopy.…”

Section: Methodsmentioning

confidence: 99%

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success

Huemer

Shambat

Bergadà-Pijuan

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus causes invasive infections and easily acquires antibiotic resistance. Even antibiotic-susceptible S. aureus can survive antibiotic therapy and persist, requiring prolonged treatment and surgical interventions. These so-called persisters display an arrested-growth phenotype, tolerate high antibiotic concentrations, and are associated with chronic and recurrent infections. To characterize these persisters, we assessed S. aureus recovered directly from a patient suffering from a persistent infection. We show that host-mediated stress, including acidic pH, abscess environment, and antibiotic exposure promoted persister formation in vitro and in vivo. Multiomics analysis identified molecular changes in S. aureus in response to acid stress leading to an overall virulent population. However, further analysis of a persister-enriched population revealed major molecular reprogramming in persisters, including down-regulation of virulence and cell division and up-regulation of ribosomal proteins, nucleotide-, and amino acid-metabolic pathways, suggesting their requirement to fuel and maintain the persister phenotype and highlighting that persisters are not completely metabolically inactive. Additionally, decreased aconitase activity and ATP levels and accumulation of insoluble proteins involved in transcription, translation, and energy production correlated with persistence in S. aureus, underpinning the molecular mechanisms that drive the persister phenotype. Upon regrowth, these persisters regained their virulence potential and metabolically active phenotype, including reduction of insoluble proteins, exhibiting a reversible state, crucial for recurrent infections. We further show that a targeted antipersister combination therapy using retinoid derivatives and antibiotics significantly reduced lag-phase heterogeneity and persisters in a murine infection model. Our results provide molecular insights into persisters and help explain why persistent S. aureus infections are so difficult to treat.

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Section: Methodsmentioning

confidence: 99%

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success

Huemer

Shambat

Bergadà-Pijuan

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Regrowth of bacteria in the zone of inhibition shows the presence of tolerant cells. For rapid detection of tolerance that were caused by an increase in lag time (tolerance by lag), such as those observed in the study of Fridman et al (2014), automated imaging with ScanLag (Levin-Reisman et al, 2010) or ColTapp (Bär et al, 2020) can be adopted.…”

Section: Clinical Detection Of Tolerant Strains To Prevent the Develomentioning

confidence: 99%

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance

Sulaiman

Lam

2021

Front. Microbiol.

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Recent laboratory evolution studies have shown that upon repetitive antibiotic treatments, bacterial populations will adapt and eventually became tolerant and resistant to the drug. Drug tolerance rapidly evolves upon frequent, intermittent antibiotic treatments, and such emerging drug tolerance seems to be specific to the treatment conditions, complicating clinical practice. Moreover, it has been shown that tolerance often promotes the development of resistance, which further reinforces the need of clinical diagnostics for antibiotic tolerance to reduce the occurrence of acquired resistance. Here, we discuss the laboratory evolution studies that were performed to track the development of tolerance in bacterial populations, and highlight the urgency of developing a comprehensive knowledge base of various tolerance phenotypes and their detection in clinics. Finally, we propose future directions for basic research in this growing field.

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“…To assess the fraction of persisters in the S. aureus clinical isolates population, an assay based on colony size distribution and bacterial survival to antibiotics upon low pH stress was conducted as previously described (32,33). Images were analyzed with ColTapp (34).…”

Section: Persister Assaymentioning

confidence: 99%

Limited adaptive evolution ofStaphylococcus aureusduring transition from colonization to invasive infection

Räz

Andreoni

Boumasmoud

et al. 2021

Preprint

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Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified and phenotypic traits are understudied. We therefore assessed pheno- and genotypic profiles of eleven S. aureus isolate pairs sampled from colonized patients simultaneously suffering from invasive S. aureus infections. Ten out of 11 isolate pairs presented the same spa and MLST suggesting colonization as origin for the invasive infection. Systematic analysis of colonizing and invasive isolate pairs showed similar adherence, hemolysis and reproductive fitness properties, minimal genetic differences, identical antibiotic tolerance and bacterial virulence in Galleria mellonella. Our results provide insights into the similar phenotype associated with limited adaptive genetic evolution between the colonizing and invasive isolates. Disruption of the physical barriers mucosa or skin were identified in the majority of patients further emphasizing colonization as a major risk factor for invasive disease.

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Efficient microbial colony growth dynamics quantification with ColTapp, an automated image analysis application

Cited by 46 publications

References 49 publications

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance

Limited adaptive evolution ofStaphylococcus aureusduring transition from colonization to invasive infection

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