Ciprofloxacin-induced persister-cells in Campylobacter jejuni.

Campylobacter jejuni is a major bacterial foodborne-pathogen. Ciprofloxacin is an important antibiotic for the treatment of C. jejuni, albeit high rates of fluoroquinolone resistance have limited its usefulness. Persister-cells are transiently antibiotic-tolerant fractions of bacterial populations and their occurrence has been associated with recalcitrant and persistent bacterial infections. Here, time-kill assays with ciprofloxacin (200×MIC, 25 µg ml-1) were performed in C. jejuni strains 81-176 and RM1221 and persister-cells were found. The frequency of survivors after 8 h of ciprofloxacin exposure was approx. 10-3 for both strains, while after 22 h the frequency was between 10-5-10-7, depending on the strain and growth-phase. Interestingly, the stationary-phase cultures did not display more persister-cells compared to exponential-phase cultures, in contrast to what has been observed in other bacterial species. Persister-cells after ampicillin exposure (100×MIC, 200 µg ml-1) were not detected, implying that persister-cell formation in C. jejuni is antibiotic-specific. In attempts to identify the mechanism of ciprofloxacin persister-cell formation, stringent or SOS responses were not found to play major roles. Overall, this study reports ciprofloxacin persister-cells in C. jejuni and challenges the notion of persister-cells as plainly dormant non-growing cells.

[1]  D. Byrne,et al.  YtfK activates the stringent response by triggering the alarmone synthetase SpoT in Escherichia coli , 2019, Nature Communications.

[2]  A. Alatas,et al.  Intrinsic anharmonic localization in thermoelectric PbSe , 2019, Nature Communications.

[3]  T. Wood,et al.  Ribosome dependence of persister cell formation and resuscitation , 2019, Journal of microbiology.

[4]  E. Fèvre,et al.  Campylobacter, a zoonotic pathogen of global importance: Prevalence and risk factors in the fast-evolving chicken meat system of Nairobi, Kenya , 2018, PLoS neglected tropical diseases.

[5]  S. Sheppard,et al.  Trends in fluoroquinolone resistance in Campylobacter , 2018, Microbial genomics.

[6]  M. Bahlo,et al.  Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific , 2018, PLoS neglected tropical diseases.

[7]  D. Goodlett,et al.  CXC Chemokines Exhibit Bactericidal Activity against Multidrug-Resistant Gram-Negative Pathogens , 2017, mBio.

[8]  Muhammad Umer Siddiqui,et al.  Immediate versus deferred stenting for patients undergoing primary or emergent percutaneous coronary intervention , 2017, Medicine.

[9]  A. Kandwal,et al.  Continuous Beam Steering Through Broadside Using Asymmetrically Modulated Goubau Line Leaky-Wave Antennas , 2017, Scientific Reports.

[10]  B. Cho,et al.  Recurrent Campylobacter jejuni bacteremia in a patient with hypogammaglobulinemia , 2017, Medicine.

[11]  R. Fisher,et al.  Persistent bacterial infections and persister cells , 2017, Nature Reviews Microbiology.

[12]  D. Chevret,et al.  Profiling of Campylobacter jejuni Proteome in Exponential and Stationary Phase of Growth , 2017, Front. Microbiol..

[13]  Lei Dai,et al.  Rising fluoroquinolone resistance in Campylobacter isolated from feedlot cattle in the United States , 2017, Scientific Reports.

[14]  F. Kong,et al.  Moraxella catarrhalis Macrolide-Resistant Isolates Are Highly Concentrated in Two MLST Clonal Complexes -CCN10 and CC363 , 2017, Front. Microbiol..

[15]  K. Lewis,et al.  ATP-Dependent Persister Formation in Escherichia coli , 2017, mBio.

[16]  T. Wood,et al.  Persistent Persister Misperceptions , 2016, Front. Microbiol..

[17]  Xun Xu,et al.  A reference gene catalogue of the pig gut microbiome , 2016, Nature Microbiology.

[18]  C. Marques,et al.  Interaction of Staphylococcus aureus persister cells with the host when in a persister state and following awakening , 2016, Scientific Reports.

[19]  T. Tenson,et al.  Persisters—as elusive as ever , 2016, Applied Microbiology and Biotechnology.

[20]  D. Hendrixson,et al.  Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization , 2016, PloS one.

[21]  Françoise Munaut,et al.  A European Database of Fusarium graminearum and F. culmorum Trichothecene Genotypes , 2016, Front. Microbiol..

[22]  T. Wood,et al.  Persistence Increases in the Absence of the Alarmone Guanosine Tetraphosphate by Reducing Cell Growth , 2016, Scientific Reports.

[23]  Endre Horváth,et al.  Controlled growth of CH3NH3PbI3 nanowires in arrays of open nanofluidic channels , 2016, Scientific Reports.

[24]  M. P. Brynildsen,et al.  Stationary-Phase Persisters to Ofloxacin Sustain DNA Damage and Require Repair Systems Only during Recovery , 2015, mBio.

[25]  Marco Alberto Javarone,et al.  Modeling Radicalization Phenomena in Heterogeneous Populations , 2015, PloS one.

[26]  Stephanie M. Amato,et al.  Persister Heterogeneity Arising from a Single Metabolic Stress , 2015, Current Biology.

[27]  J. Veening,et al.  The ParB-parS Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae , 2015, mBio.

[28]  Tanel Tenson,et al.  Recent functional insights into the role of (p)ppGpp in bacterial physiology , 2015, Nature Reviews Microbiology.

[29]  B. Levin,et al.  Persistence: a copacetic and parsimonious hypothesis for the existence of non-inherited resistance to antibiotics. , 2014, Current opinion in microbiology.

[30]  D. Bumann,et al.  Phenotypic Variation of Salmonella in Host Tissues Delays Eradication by Antimicrobial Chemotherapy , 2014, Cell.

[31]  K. Gerdes,et al.  Molecular Mechanisms Underlying Bacterial Persisters , 2014, Cell.

[32]  Byeonghwa Jeon A tangle of poly-phosphate in Campylobacter , 2014, Virulence.

[33]  G. Reid,et al.  Selective Target Inactivation Rather than Global Metabolic Dormancy Causes Antibiotic Tolerance in Uropathogens , 2014, Antimicrobial Agents and Chemotherapy.

[34]  K. Gerdes,et al.  RETRACTED: (p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity , 2013, Cell.

[35]  L. Ellerbroek,et al.  Serotype Distribution of Salmonella Isolates from Turkey Ground Meat and Meat Parts , 2013, BioMed research international.

[36]  J. Osek,et al.  Antimicrobial Resistance Mechanisms among Campylobacter , 2013, BioMed research international.

[37]  J. Collins,et al.  Microbial persistence and the road to drug resistance. , 2013, Cell host & microbe.

[38]  Mehmet A. Orman,et al.  Dormancy Is Not Necessary or Sufficient for Bacterial Persistence , 2013, Antimicrobial Agents and Chemotherapy.

[39]  E. van Nimwegen,et al.  Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli , 2013, BMC Microbiology.

[40]  M. Palmer,et al.  Community terminal restriction fragment length polymorphisms reveal insights into the diversity and dynamics of leaf endophytic bacteria , 2013, BMC Microbiology.

[41]  C. Lévesque,et al.  A Stress-Inducible Quorum-Sensing Peptide Mediates the Formation of Persister Cells with Noninherited Multidrug Tolerance , 2012, Journal of bacteriology.

[42]  F. Lépine,et al.  Active Starvation Responses Mediate Antibiotic Tolerance in Biofilms and Nutrient-Limited Bacteria , 2011, Science.

[43]  Robert J. Moore,et al.  Necrotic Enteritis-Derived Clostridium perfringens Strain with Three Closely Related Independently Conjugative Toxin and Antibiotic Resistance Plasmids , 2011, mBio.

[44]  E. Rubin,et al.  Characterization and Transcriptome Analysis of Mycobacterium tuberculosis Persisters , 2011, mBio.

[45]  Jan Michiels,et al.  Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. , 2011, Journal of medical microbiology.

[46]  T. Tenson,et al.  Age of Inoculum Strongly Influences Persister Frequency and Can Mask Effects of Mutations Implicated in Altered Persistence , 2011, Journal of bacteriology.

[47]  W. Shi,et al.  Energy production genes sucB and ubiF are involved in persister survival and tolerance to multiple antibiotics and stresses in Escherichia coli. , 2010, FEMS microbiology letters.

[48]  C. Dean,et al.  Pseudomonas aeruginosa Increases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules , 2010, Journal of bacteriology.

[49]  C. Parker,et al.  Nucleases Encoded by the Integrated Elements CJIE2 and CJIE4 Inhibit Natural Transformation of Campylobacter jejuni , 2009, Journal of bacteriology.

[50]  M. Vulić,et al.  SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli , 2009, PLoS genetics.

[51]  I. Jackson,et al.  Palmitoylation Regulates Epidermal Homeostasis and Hair Follicle Differentiation , 2009, PLoS Genetics.

[52]  S. Lovett,et al.  The Stringent Response and Cell Cycle Arrest in Escherichia coli , 2008, PLoS genetics.

[53]  Giovanni Cenci,et al.  Identification of Drosophila Mitotic Genes by Combining Co-Expression Analysis and RNA Interference , 2008, PLoS genetics.

[54]  Nathalie Q Balaban,et al.  Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria , 2008, Proceedings of the National Academy of Sciences.

[55]  M. Vulić,et al.  GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli , 2006, Journal of bacteriology.

[56]  B. Levin,et al.  Non-inherited antibiotic resistance , 2006, Nature Reviews Microbiology.

[57]  Arkady Khodursky,et al.  Persisters: a distinct physiological state of E. coli , 2006, BMC Microbiology.

[58]  A. Moya,et al.  Analysis of and function predictions for previously conserved hypothetical or putative proteins in Blochmannia floridanus , 2006, BMC Microbiology.

[59]  S. Falkow,et al.  The Campylobacter jejuni stringent response controls specific stress survival and virulence‐associated phenotypes , 2005, Molecular microbiology.

[60]  K. Jordan,et al.  Induction of an adaptive tolerance response in the foodborne pathogen, Campylobacter jejuni. , 2003, FEMS microbiology letters.

[61]  K. Lewis,et al.  Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials , 2001, Journal of bacteriology.

[62]  A. F. Kelly,et al.  Survival of Campylobacter jejuniduring Stationary Phase: Evidence for the Absence of a Phenotypic Stationary-Phase Response , 2001, Applied and Environmental Microbiology.

[63]  R. Mandrell,et al.  Detection on Surfaces and in Caco-2 Cells of Campylobacter jejuni Cells Transformed with New gfp, yfp, andcfp Marker Plasmids , 2000, Applied and Environmental Microbiology.

[64]  B. Barrell,et al.  The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences , 2000, Nature.

[65]  J. Adkins,et al.  Persister formation in Staphylococcus aureus is associated with ATP depletion. , 2016, Nature microbiology.

[66]  K. Lewis,et al.  Persister cells and tolerance to antimicrobials. , 2004, FEMS microbiology letters.

[67]  M. Ferraro Performance standards for antimicrobial susceptibility testing , 2001 .