The impact of physiological state and environmental stress on bacterial load estimation methodologies for Mycobacterium tuberculosis

When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase...

Full description

Saved in:
Bibliographic Details
Published inScientific reports Vol. 14; no. 1; pp. 26108 - 8
Main Authors Maitra, Arundhati, Wijk, Marie, Margaryan, Hasmik, Denti, Paolo, McHugh, Timothy D., Kloprogge, Frank
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.10.2024
Nature Portfolio
Subjects
631/326/22/1290
631/326/2521
692/308/2778
692/53/2421
692/699/255/1856
Bacterial Load
Colony Count, Microbial
Early bactericidal activity
Humanities and Social Sciences
Humans
Isoniazid - pharmacology
multidisciplinary
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - physiology
Rifampin - pharmacology
Science
Science (multidisciplinary)
Stress, Physiological
Tuberculosis
Tuberculosis - drug therapy
Tuberculosis - microbiology
Early bactericidal activity
Tuberculosis
Online AccessGet full text

Cover

Abstract When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.
AbstractList When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.
When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.
When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.
Abstract When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture. The bacterial load was estimated by colony counts and the BD BACTEC MGIT system. Linear and nonlinear mixed-effects models were used to describe the relationship between time-to-positivity (TTP) and time-to-growth (TTG) versus colony forming units (CFU), and growth units (GU) versus incubation time in MGIT. For samples with the same CFU, antibiotic-treated and stationary phase cells had a shorter TTP than antibiotic-free controls and early-logarithmic phase cells, respectively. Similarly, stationary phase samples reached higher GUs and had shorter TTG than early-log phase ones. This suggests that there is a population of bacterial cells that can be differentially recovered in liquid medium, giving us insight into the physiological states of the original culture, aiding the interpretation of clinical trial outputs.
ArticleNumber 26108
Author Maitra, Arundhati
Kloprogge, Frank
Denti, Paolo
McHugh, Timothy D.
Margaryan, Hasmik
Wijk, Marie
Author_xml – sequence: 1
  givenname: Arundhati
  surname: Maitra
  fullname: Maitra, Arundhati
  organization: Institute for Global Health, University College London, Centre for Clinical Microbiology, University College London
– sequence: 2
  givenname: Marie
  surname: Wijk
  fullname: Wijk, Marie
  email: sjlmar001@myuct.ac.za
  organization: Institute for Global Health, University College London, Division of Clinical Pharmacology, Department of Medicine, University of Cape Town
– sequence: 3
  givenname: Hasmik
  surname: Margaryan
  fullname: Margaryan, Hasmik
  organization: Centre for Clinical Microbiology, University College London
– sequence: 4
  givenname: Paolo
  surname: Denti
  fullname: Denti, Paolo
  organization: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town
– sequence: 5
  givenname: Timothy D.
  surname: McHugh
  fullname: McHugh, Timothy D.
  organization: Centre for Clinical Microbiology, University College London
– sequence: 6
  givenname: Frank
  surname: Kloprogge
  fullname: Kloprogge, Frank
  email: f.kloprogge@ucl.ac.uk
  organization: Institute for Global Health, University College London, Centre for Clinical Microbiology, University College London
BackLink https://www.ncbi.nlm.nih.gov/pubmed/39477982$$D View this record in MEDLINE/PubMed
BookMark eNp9Uk1v1DAQjVARLaV_gAPykUvAn4lzQqjio1IRl3K2bGe861ViL7ZTae_94ZjNUrUXfLE1896b8cx73ZyFGKBp3hL8gWAmP2ZOxCBbTHnbc0Zky140FxRz0VJG6dmT93lzlfMO1yPowMnwqjlnA-_7QdKL5uFuC8jPe20Lig7tt4fs4xQ33uoJ5aILIB1GBOHepxhmCOUYT5AzigGZyoPka2yKusJy8bMuvmZmKNs4HqUgIxcT-nGw8YRfZlQWA8kuU8w-v2leOj1luDrdl82vr1_urr-3tz-_3Vx_vm0t73hpO8m47Ou_pOtHwAyYMNAxLAwFDnbomXTU2prExnJJtOk66joykN4YKYFdNjer7hj1Tu1T7TUdVNReHQMxbZROxdsJlGaUdFrCwO3Ie-akM0xgARi4AONk1fq0au0XM8No62SSnp6JPs8Ev1WbeK8IEVRI3FWF9yeFFH8vdXRq9tnCNOkAccmKEUo7zhnrK_Td02KPVf7tsQLoCrAp5pzAPUIIVn_9ola_qOoXdfSLYpXEVlKu4LCBpHZxSaFu4H-sPzKTxnI
Cites_doi 10.1126/science.1216166
10.1111/j.1469-0691.2011.03626.x
10.1073/pnas.1705385114
10.1016/j.cmpb.2003.11.003
10.1007/s10096-010-1043-7
10.1186/s12916-017-0955-9
10.1016/j.tube.2011.01.004
10.1038/nrmicro1460
10.1093/jac/dku415
10.1038/ncomms3470
10.1016/j.tube.2013.08.003
10.1093/jac/dkt357
10.1038/psp.2013.24
10.1371/journal.pone.0044582
10.1038/nrmicro3299
10.1111/mmi.12169
10.1038/s41598-021-98176-5
10.1128/9781555819569.ch32
10.1164/rccm.200905-0661OC
10.1007/978-0-387-75936-4
ContentType Journal Article
Copyright The Author(s) 2024
2024. The Author(s).
The Author(s) 2024 2024
Copyright_xml – notice: The Author(s) 2024
– notice: 2024. The Author(s).
– notice: The Author(s) 2024 2024
DBID C6C
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7X8
5PM
DOA
DOI 10.1038/s41598-024-74318-3
DatabaseName SpringerOpen Free (Free internet resource, activated by CARLI)
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList CrossRef
MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: C6C
  name: SpringerOpen Free (Free internet resource, activated by CARLI)
  url: http://www.springeropen.com/
  sourceTypes: Publisher
– sequence: 2
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 3
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 4
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2045-2322
EndPage 8
ExternalDocumentID oai_doaj_org_article_a3216a8e94cd473f8fb3505e0e45ebf8
PMC11525806
39477982
10_1038_s41598_024_74318_3
Genre Journal Article
GrantInformation_xml – fundername: Wellcome Trust
  grantid: 220587/Z/20/Z
  funderid: http://dx.doi.org/10.13039/100010269
– fundername: Wellcome Trust
– fundername: Wellcome Trust
  grantid: 220587/Z/20/Z
GroupedDBID 0R~
4.4
53G
5VS
7X7
88E
88I
8FE
8FH
8FI
8FJ
AAFWJ
AAJSJ
AAKDD
AASML
ABDBF
ABUWG
ACGFS
ACUHS
ADBBV
ADRAZ
AENEX
AEUYN
AFKRA
AFPKN
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AOIJS
AZQEC
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
C6C
CCPQU
DIK
DWQXO
EBD
EBLON
EBS
ESX
FYUFA
GNUQQ
GROUPED_DOAJ
GX1
HCIFZ
HH5
HMCUK
HYE
KQ8
LK8
M1P
M2P
M48
M7P
M~E
NAO
OK1
PHGZM
PHGZT
PIMPY
PJZUB
PPXIY
PQGLB
PQQKQ
PROAC
PSQYO
RNT
RNTTT
RPM
SNYQT
UKHRP
AAYXX
CITATION
3V.
88A
ACSMW
AJTQC
CGR
CUY
CVF
ECM
EIF
M0L
NPM
7X8
5PM
PUEGO
ID FETCH-LOGICAL-c464t-6834872048f7de03e35be6305b2e4ec9738f2ccf7d0bc481ab662f61917bb88e3
IEDL.DBID M48
ISSN 2045-2322
IngestDate Wed Aug 27 01:28:46 EDT 2025
Thu Aug 21 18:43:55 EDT 2025
Fri Jul 11 09:15:29 EDT 2025
Wed Feb 19 02:15:45 EST 2025
Tue Jul 01 03:23:24 EDT 2025
Mon Jul 21 06:08:09 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1
Keywords Early bactericidal activity
Tuberculosis
Language English
License 2024. The Author(s).
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c464t-6834872048f7de03e35be6305b2e4ec9738f2ccf7d0bc481ab662f61917bb88e3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1038/s41598-024-74318-3
PMID 39477982
PQID 3122644337
PQPubID 23479
PageCount 8
ParticipantIDs doaj_primary_oai_doaj_org_article_a3216a8e94cd473f8fb3505e0e45ebf8
pubmedcentral_primary_oai_pubmedcentral_nih_gov_11525806
proquest_miscellaneous_3122644337
pubmed_primary_39477982
crossref_primary_10_1038_s41598_024_74318_3
springer_journals_10_1038_s41598_024_74318_3
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2024-10-30
PublicationDateYYYYMMDD 2024-10-30
PublicationDate_xml – month: 10
  year: 2024
  text: 2024-10-30
  day: 30
PublicationDecade 2020
PublicationPlace London
PublicationPlace_xml – name: London
– name: England
PublicationTitle Scientific reports
PublicationTitleAbbrev Sci Rep
PublicationTitleAlternate Sci Rep
PublicationYear 2024
Publisher Nature Publishing Group UK
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Portfolio
References SaitoKRifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populationsProc. Natl. Acad. Sci.2017114E4832E48401:CAS:528:DC%2BC2sXovVSisr4%3D10.1073/pnas.170538511428559332
MukamolovaGVTurapovOMalkinJWoltmannGBarerMRResuscitation-promoting factors reveal an occult population of tubercle bacilli in sputumAm. J. Respir. Crit. Care Med.20101811741801:CAS:528:DC%2BC3cXhvFahu7o%3D10.1164/rccm.200905-0661OC19875686
Dhar, N., McKinney, J. & Manina, G. Phenotypic heterogeneity in Mycobacterium tuberculosis. Tuberc. Tuber. Bacillus 671–697 (2017).
Chambers, J. M. Software for data analysis: Programming with R. vol. 2 (Springer, 2008).
JindaniAAberVREdwardsEAMitchisonDAThe early bactericidal activity of drugs in patients with pulmonary tuberculosisAm. Rev. Respir. Dis.19801219399491:STN:280:DyaL3M%2FhvFygtw%3D%3D6774638
BarrDAFlow cytometry method for absolute counting and single-cell phenotyping of mycobacteriaSci. Rep.202111186612021NatSR..1118661B1:CAS:528:DC%2BB3MXitFagtrjN10.1038/s41598-021-98176-534545154
Joyce, G. et al. Cell division site placement and asymmetric growth in mycobacteria. (2012).
LindbomLRibbingJJonssonENPerl-speaks-NONMEM (PsN)—A Perl module for NONMEM related programmingComput. Methods Programs Biomed.200475859410.1016/j.cmpb.2003.11.00315212851
CaceresNEvolution and role of corded cell aggregation in Mycobacterium tuberculosis culturesTuberculosis2013936906981:CAS:528:DC%2BC3sXhsVKgtbzE10.1016/j.tube.2013.08.00324011631
BownessRThe relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populationsJ. Antimicrob. Chemother.2015704484551:CAS:528:DC%2BC2MXivFGmtb8%3D10.1093/jac/dku41525344806
AverySVMicrobial cell individuality and the underlying sources of heterogeneityNat. Rev. Microbiol.200645775871:CAS:528:DC%2BD28XmvFamtbs%3D10.1038/nrmicro146016845428
SantiIDharNBousbaineDWakamotoYMcKinneyJDSingle-cell dynamics of the chromosome replication and cell division cycles in mycobacteriaNat. Commun.2013424702013NatCo...4.2470S10.1038/ncomms347024036848
KieserKJRubinEJHow sisters grow apart: Mycobacterial growth and divisionNat. Rev. Microbiol.2014125505621:CAS:528:DC%2BC2cXhtFSlsLnL10.1038/nrmicro3299249987396556109
AldridgeBBAsymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibilityScience20123351001042012Sci...335..100A1:CAS:528:DC%2BC38Xns1Ci10.1126/science.121616622174129
KeizerRJKarlssonMOHookerAModeling and simulation workbench for NONMEM: Tutorial on Pirana, PsN, and XposeCPT Pharmacomet. Syst. Pharmacol.201321910.1038/psp.2013.24
MitchisonDAStrumAWThe measurement of early bactericidal activityBaillières Clin. Infect. Dis.19974185206
SinghBAsymmetric growth and division in M ycobacterium spp.: Compensatory mechanisms for non-medial septaMol. Microbiol.20138864761:CAS:528:DC%2BC3sXksFSqu7g%3D10.1111/mmi.1216923387305
WHO. Global tuberculosis report 2023. (2023).
DiaconAHTime to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agentsEur. J. Clin. Microbiol. Infect. Dis.201029156115651:CAS:528:DC%2BC3cXhsV2gtbzK10.1007/s10096-010-1043-720820832
Boeckmann, A. J., Sheiner, L. B. & Beal, S. L. NONMEM User’s Guide, Part V. Introductory Guide. p 48. (2011).
DhillonJFouriePBMitchisonDAPersister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture mediaJ. Antimicrob. Chemother.2014694374401:CAS:528:DC%2BC2cXlvFOktQ%3D%3D10.1093/jac/dkt35724072170
DiaconAHTime to liquid culture positivity can substitute for colony counting on agar plates in early bactericidal activity studies of antituberculosis agentsClin. Microbiol. Infect.2012187117171:CAS:528:DC%2BC38XhtFOhtrrL10.1111/j.1469-0691.2011.03626.x21851489
PhillipsPPJA comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimensBMC Med.2017151910.1186/s12916-017-0955-9
BarkCMTime to detection of Mycobacterium tuberculosis as an alternative to quantitative culturesTuberculosis2011912572591:STN:280:DC%2BC3MvptVajsw%3D%3D10.1016/j.tube.2011.01.00421353641
K Saito (74318_CR8) 2017; 114
BB Aldridge (74318_CR15) 2012; 335
DA Mitchison (74318_CR3) 1997; 4
L Lindbom (74318_CR23) 2004; 75
R Bowness (74318_CR11) 2015; 70
SV Avery (74318_CR19) 2006; 4
A Jindani (74318_CR2) 1980; 121
PPJ Phillips (74318_CR7) 2017; 15
DA Barr (74318_CR13) 2021; 11
74318_CR20
CM Bark (74318_CR6) 2011; 91
N Caceres (74318_CR12) 2013; 93
74318_CR1
J Dhillon (74318_CR9) 2014; 69
B Singh (74318_CR17) 2013; 88
KJ Kieser (74318_CR14) 2014; 12
74318_CR16
AH Diacon (74318_CR5) 2012; 18
GV Mukamolova (74318_CR10) 2010; 181
74318_CR21
AH Diacon (74318_CR4) 2010; 29
74318_CR24
I Santi (74318_CR18) 2013; 4
RJ Keizer (74318_CR22) 2013; 2
References_xml – reference: Dhar, N., McKinney, J. & Manina, G. Phenotypic heterogeneity in Mycobacterium tuberculosis. Tuberc. Tuber. Bacillus 671–697 (2017).
– reference: MukamolovaGVTurapovOMalkinJWoltmannGBarerMRResuscitation-promoting factors reveal an occult population of tubercle bacilli in sputumAm. J. Respir. Crit. Care Med.20101811741801:CAS:528:DC%2BC3cXhvFahu7o%3D10.1164/rccm.200905-0661OC19875686
– reference: WHO. Global tuberculosis report 2023. (2023).
– reference: SantiIDharNBousbaineDWakamotoYMcKinneyJDSingle-cell dynamics of the chromosome replication and cell division cycles in mycobacteriaNat. Commun.2013424702013NatCo...4.2470S10.1038/ncomms347024036848
– reference: BarrDAFlow cytometry method for absolute counting and single-cell phenotyping of mycobacteriaSci. Rep.202111186612021NatSR..1118661B1:CAS:528:DC%2BB3MXitFagtrjN10.1038/s41598-021-98176-534545154
– reference: Boeckmann, A. J., Sheiner, L. B. & Beal, S. L. NONMEM User’s Guide, Part V. Introductory Guide. p 48. (2011).
– reference: DhillonJFouriePBMitchisonDAPersister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture mediaJ. Antimicrob. Chemother.2014694374401:CAS:528:DC%2BC2cXlvFOktQ%3D%3D10.1093/jac/dkt35724072170
– reference: AldridgeBBAsymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibilityScience20123351001042012Sci...335..100A1:CAS:528:DC%2BC38Xns1Ci10.1126/science.121616622174129
– reference: KieserKJRubinEJHow sisters grow apart: Mycobacterial growth and divisionNat. Rev. Microbiol.2014125505621:CAS:528:DC%2BC2cXhtFSlsLnL10.1038/nrmicro3299249987396556109
– reference: SaitoKRifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populationsProc. Natl. Acad. Sci.2017114E4832E48401:CAS:528:DC%2BC2sXovVSisr4%3D10.1073/pnas.170538511428559332
– reference: CaceresNEvolution and role of corded cell aggregation in Mycobacterium tuberculosis culturesTuberculosis2013936906981:CAS:528:DC%2BC3sXhsVKgtbzE10.1016/j.tube.2013.08.00324011631
– reference: DiaconAHTime to liquid culture positivity can substitute for colony counting on agar plates in early bactericidal activity studies of antituberculosis agentsClin. Microbiol. Infect.2012187117171:CAS:528:DC%2BC38XhtFOhtrrL10.1111/j.1469-0691.2011.03626.x21851489
– reference: MitchisonDAStrumAWThe measurement of early bactericidal activityBaillières Clin. Infect. Dis.19974185206
– reference: KeizerRJKarlssonMOHookerAModeling and simulation workbench for NONMEM: Tutorial on Pirana, PsN, and XposeCPT Pharmacomet. Syst. Pharmacol.201321910.1038/psp.2013.24
– reference: SinghBAsymmetric growth and division in M ycobacterium spp.: Compensatory mechanisms for non-medial septaMol. Microbiol.20138864761:CAS:528:DC%2BC3sXksFSqu7g%3D10.1111/mmi.1216923387305
– reference: Joyce, G. et al. Cell division site placement and asymmetric growth in mycobacteria. (2012).
– reference: DiaconAHTime to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agentsEur. J. Clin. Microbiol. Infect. Dis.201029156115651:CAS:528:DC%2BC3cXhsV2gtbzK10.1007/s10096-010-1043-720820832
– reference: BarkCMTime to detection of Mycobacterium tuberculosis as an alternative to quantitative culturesTuberculosis2011912572591:STN:280:DC%2BC3MvptVajsw%3D%3D10.1016/j.tube.2011.01.00421353641
– reference: BownessRThe relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populationsJ. Antimicrob. Chemother.2015704484551:CAS:528:DC%2BC2MXivFGmtb8%3D10.1093/jac/dku41525344806
– reference: AverySVMicrobial cell individuality and the underlying sources of heterogeneityNat. Rev. Microbiol.200645775871:CAS:528:DC%2BD28XmvFamtbs%3D10.1038/nrmicro146016845428
– reference: LindbomLRibbingJJonssonENPerl-speaks-NONMEM (PsN)—A Perl module for NONMEM related programmingComput. Methods Programs Biomed.200475859410.1016/j.cmpb.2003.11.00315212851
– reference: JindaniAAberVREdwardsEAMitchisonDAThe early bactericidal activity of drugs in patients with pulmonary tuberculosisAm. Rev. Respir. Dis.19801219399491:STN:280:DyaL3M%2FhvFygtw%3D%3D6774638
– reference: PhillipsPPJA comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimensBMC Med.2017151910.1186/s12916-017-0955-9
– reference: Chambers, J. M. Software for data analysis: Programming with R. vol. 2 (Springer, 2008).
– volume: 335
  start-page: 100
  year: 2012
  ident: 74318_CR15
  publication-title: Science
  doi: 10.1126/science.1216166
– volume: 18
  start-page: 711
  year: 2012
  ident: 74318_CR5
  publication-title: Clin. Microbiol. Infect.
  doi: 10.1111/j.1469-0691.2011.03626.x
– volume: 114
  start-page: E4832
  year: 2017
  ident: 74318_CR8
  publication-title: Proc. Natl. Acad. Sci.
  doi: 10.1073/pnas.1705385114
– volume: 75
  start-page: 85
  year: 2004
  ident: 74318_CR23
  publication-title: Comput. Methods Programs Biomed.
  doi: 10.1016/j.cmpb.2003.11.003
– volume: 29
  start-page: 1561
  year: 2010
  ident: 74318_CR4
  publication-title: Eur. J. Clin. Microbiol. Infect. Dis.
  doi: 10.1007/s10096-010-1043-7
– volume: 15
  start-page: 1
  year: 2017
  ident: 74318_CR7
  publication-title: BMC Med.
  doi: 10.1186/s12916-017-0955-9
– volume: 4
  start-page: 185
  year: 1997
  ident: 74318_CR3
  publication-title: Baillières Clin. Infect. Dis.
– ident: 74318_CR1
– volume: 121
  start-page: 939
  year: 1980
  ident: 74318_CR2
  publication-title: Am. Rev. Respir. Dis.
– volume: 91
  start-page: 257
  year: 2011
  ident: 74318_CR6
  publication-title: Tuberculosis
  doi: 10.1016/j.tube.2011.01.004
– volume: 4
  start-page: 577
  year: 2006
  ident: 74318_CR19
  publication-title: Nat. Rev. Microbiol.
  doi: 10.1038/nrmicro1460
– volume: 70
  start-page: 448
  year: 2015
  ident: 74318_CR11
  publication-title: J. Antimicrob. Chemother.
  doi: 10.1093/jac/dku415
– volume: 4
  start-page: 2470
  year: 2013
  ident: 74318_CR18
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms3470
– volume: 93
  start-page: 690
  year: 2013
  ident: 74318_CR12
  publication-title: Tuberculosis
  doi: 10.1016/j.tube.2013.08.003
– volume: 69
  start-page: 437
  year: 2014
  ident: 74318_CR9
  publication-title: J. Antimicrob. Chemother.
  doi: 10.1093/jac/dkt357
– volume: 2
  start-page: 1
  year: 2013
  ident: 74318_CR22
  publication-title: CPT Pharmacomet. Syst. Pharmacol.
  doi: 10.1038/psp.2013.24
– ident: 74318_CR16
  doi: 10.1371/journal.pone.0044582
– volume: 12
  start-page: 550
  year: 2014
  ident: 74318_CR14
  publication-title: Nat. Rev. Microbiol.
  doi: 10.1038/nrmicro3299
– volume: 88
  start-page: 64
  year: 2013
  ident: 74318_CR17
  publication-title: Mol. Microbiol.
  doi: 10.1111/mmi.12169
– ident: 74318_CR21
– volume: 11
  start-page: 18661
  year: 2021
  ident: 74318_CR13
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-021-98176-5
– ident: 74318_CR20
  doi: 10.1128/9781555819569.ch32
– volume: 181
  start-page: 174
  year: 2010
  ident: 74318_CR10
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/rccm.200905-0661OC
– ident: 74318_CR24
  doi: 10.1007/978-0-387-75936-4
SSID ssj0000529419
Score 2.4377024
Snippet When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of...
Abstract When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the...
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 26108
SubjectTerms 631/326/22/1290
631/326/2521
692/308/2778
692/53/2421
692/699/255/1856
Bacterial Load
Colony Count, Microbial
Early bactericidal activity
Humanities and Social Sciences
Humans
Isoniazid - pharmacology
multidisciplinary
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - physiology
Rifampin - pharmacology
Science
Science (multidisciplinary)
Stress, Physiological
Tuberculosis
Tuberculosis - drug therapy
Tuberculosis - microbiology
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Ni9UwEA-yIHgRv-36QQRvGrbNpGl6VHFZhPXkwt5Ckk5wYW1l-3rYu3-4k6RveU9FL16T0KaZyXw0-f2Gsdcqoos-dCJQdC5UjLXwdUQhoY0AID3kW5Wnn_XJmfp03p7vlPpKd8IKPXBZuCMHstHOYK_CoDqIJnogr401qhZ9zDBf8nk7yVRh9Za9avoVJVODOZrJUyU0mVQiOU0jYM8TZcL-P0WZv1-W_OXENDui43vs7hpB8ndl5vfZLRwfsNulpuT1Q_aDBM8L9pFPkec_F1sDxzN8iLtx4DsAt9yesm4-jdwX9mZqu5wcDSMLUMCNvNSazo_CmVOsy0-vw7SOX77xzeLxKiyX03wxP2Jnxx-_fDgRa6kFEZRWG6ENUOaSSHxjN2ANCK1HTbbAS1QY-g5MlCFQZ-2DMo3zWsuoU7LnvTEIj9nBOI34lPEhDtqp0CKNUOT6vGxNDBRp9TI413cVe7Nddvu9MGrYfBIOxhYhWRKSzUKyULH3STI3IxMbdm4gHbGrjth_6UjFXm3lamn3pCMRN-K0zBaaBCRWADStJ0XON6-CXnVdb2TFzJ4G7M1lv2e8-JoZuptUVcrUumJvt8piV9sw_-VjD__Hxz5jd2TS8uRf6-fsYHO14AsKnDb-Zd4jPwHPCBii
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: HAS SpringerNature Open Access 2022
  dbid: AAJSJ
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3Nb9UwDI_GJiQuiG_Kl4LEDSraOE3T4wMxTU8aF5i0W5SkDkzaWvT6etidPxwnbZ94MCFxTd02rR3bif2zGXsjA9rgfJ178s5zGUKRuyJgLqAKACAcpKzK08_q5Eyuz6vzAyYWLExK2k8lLZOaXrLD3g9kaCIYTMg82jydwy12FEu1k2wfrVbrL-vdyUqMXcmymREyBegbbt6zQqlY_00e5t-Jkn9ES5MROr7H7s7eI19N873PDrB7wG5P_SSvH7KfxHQ-4R55H3g6tViUG0_QIW67lv8GbkvjccfN-467qXIzjV32lsho9U_ARj71mU6PwoGTn8tPr30_049XfDs63Pjxsh8uhkfs7PjT148n-dxmIfdSyW2uNNCuJRbwDXWLBSBUDhXpASdQom9q0EF4TxcL56UurVNKBBU3es5pjfCYHXZ9h08Zb0OrrPQVEoUks-dEpYMnL6sR3tqmztjb5bebH1M1DZOi4KDNxCRDTDKJSQYy9iFyZkcZK2GngX7zzcySYSyIUlmNjfStrCHo4IC8OixQVuiCztjrha-GVk4Mh9gO-3EwUEYQsQSgaT2Z-Lx7FTSyrhstMqb3JGBvLvtXuovvqTp3GTtK6UJl7N0iLGbWC8M_PvbZ_5E_Z3dElOdoRYsX7HC7GfEluUdb92peD78Ai5UO0w
  priority: 102
  providerName: Springer Nature
Title The impact of physiological state and environmental stress on bacterial load estimation methodologies for Mycobacterium tuberculosis
URI https://link.springer.com/article/10.1038/s41598-024-74318-3
https://www.ncbi.nlm.nih.gov/pubmed/39477982
https://www.proquest.com/docview/3122644337
https://pubmed.ncbi.nlm.nih.gov/PMC11525806
https://doaj.org/article/a3216a8e94cd473f8fb3505e0e45ebf8
Volume 14
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3di9QwEA_3geCL-G1PXSL4ptVukibpg8jecsexsIeoC_sWmjTRg7X1tltw3_3DnSTt4eoi-FSYDmmamWR-k2RmEHrJnC2dNiI1gM5T5lyW6szZlNDcUUqJpuFW5fySXyzYbJkvD9BQ7qgfwHava-frSS3Wqzc_rrfvYcK_iyHj8m0LRsgHihGWensoU3qIjsEyCV_RYN7D_ZjrmxQs1PrwSdihP4T0cTT7m9mxVSGl_z4c-vd1yj_OVIOpOr-L7vQYE0-iUtxDB7a-j27FqpPbB-gnqAaO0ZG4cTjsbQxLIA4BRrisK_xbCFyge78cNzXWMb8z0FZNCWywRsTwRxyrUYembIsBDeP51jQ9f_cNbzpt16ZbNe1V-xAtzs8-Ty_SvhhDahhnm5RLCr6NT_PrRGUzammuLYfVQhPLrCkElY4YAy8zbZgcl5pz4rh3B7WW0tJH6KhuavsE4cpVvGQmt8DBwDhqkktnAIsVxJRlIRL0ahh29T3m3FDhrJxKFYWkQEgqCEnRBJ16ydxw-nzZgdCsv6h--qmSkjEvpS2YqZigTjpNAfvZzLLcaicT9GKQq4L55Q9Nyto2Xavo2IcaM0qhW4-jnG8-RQsmRCFJguSOBuz0ZfdNffU15PAe-7pTMuMJej0oixqU_x8_e_JfQ_MU3SZenb2pzZ6ho826s88BQ230CB2KpRih48lk9mkGz9Ozyw8fgTrl01HYlxiFqfMLM7weVw
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELZKEaIXxLvhaSQ4QURiO45z4AAL1ZZ2e2ql3oztHUOlkqDNRmjv_BJ-KWMnWbFQIXHo1R45juf1-TEzhDwXHoy3rkwdovNUeJ-lNvOQMl54zjmzPL6qnB3J6Yn4eFqcbpGfYyxMfLQfU1pGMz2-DnvdoqMJwWBMpMHnqXQsWH0Aq--4TWvf7L9Hnr5gbO_D8WSaDpUEUiekWKZScQTmIUetL-eQceCFBYmibhkIcFXJlWfOYWdmnVC5sVIyL8NexlqlgOO4V8hVxPYyaM5ETtbnOOGmTOTVEI-TcXXBVDd8XiwNcBGe_ftZ5h93s9Hl7d0kNwasSt_2q3OLbEF9m1zrq1eu7pAfKGK0j7KkjafxjGQ0pTQGKlFTz-lvoXSxPezvaVNT2-eJxrbzxiAZ2po-jJL2Va3jUNBSRNV0tnLNQN99pcvOwsJ150171t4lJ5fCintku25q2CV07ufSCFcAUgh0spYVyjvEdBVzxlRlQl6Oy66_9bk7dLxz50r3TNLIJB2ZpHlC3gXOrClD3u3Y0Cw-60EOteEsl0ZBJdxclNwrbzliSMhAFGC9Ssizka8a9TRcvpgamq7VPA8hy4JznNb9ns_rT_FKlGWlWELUhgRszGWzpz77EnOB56F-lcpkQl6NwqIHK9T-42cf_B_5U3J9ejw71If7RwcPyQ4Lsh38d_aIbC8XHTxGYLa0T6JmUPLpslXxF4BdSgU
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB6VrUBcEG_C00hwgqiJ7STOgcNCWbVbWiFBpd6M7dhQqSRosxHaO7-F38nYSVYsVEgcerVHjuMZez57XgDPuLPKaVPEBtF5zJ1LYp04G1OWOcYY1Sx4VR4e5XvHfH6SnWzBzzEWJjjth5SW4ZgevcN2WlQ0PhiM8tjrPBHjFbBygzPlgV19x6ta-2p_F_n6nNLZ249v9uKhmkBseM6XcS4YgnOfp9YVlU2YZZm2OYq7ppZbUxZMOGoMdibacJEqnefU5f4-o7UQluG4l2Ab8X3KJ7A9nc4_zNevOd5extNyiMpJmDhnwhuaLxQIOA_V_u2c-YeFNii-2XW4NiBWMu3X6AZs2fomXO5rWK5uwQ8UNNLHWpLGkfBSMh6oJIQrEVVX5LeAutDub_mkqYnus0Vj21mjkAxPnD6YkvS1rcNQtiWIrcnhyjQDffeVLDttF6Y7a9rT9jYcXwgz7sCkbmp7D0jlqlxxk1mk4KhqNc2EM4jsSmqUKosIXozLLr_1GTxksLwzIXsmSWSSDEySLILXnjNrSp99OzQ0i89ykEapGE1zJWzJTcUL5oTTDJGkTSzPrHYigqcjXyXuVm-CUbVtulay1Acuc8ZwWnd7Pq8_xUpeFKWgEYgNCdiYy2ZPffolZARPfRUrkeQRvByFRQ5nUfuPn73_f-RP4Mr73Zl8t3908ACuUi_aXoknD2GyXHT2EaKzpX48bA0Cny56N_4CsVhMaQ
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+impact+of+physiological+state+and+environmental+stress+on+bacterial+load+estimation+methodologies+for+Mycobacterium+tuberculosis&rft.jtitle=Scientific+reports&rft.au=Maitra%2C+Arundhati&rft.au=Wijk%2C+Marie&rft.au=Margaryan%2C+Hasmik&rft.au=Denti%2C+Paolo&rft.date=2024-10-30&rft.issn=2045-2322&rft.eissn=2045-2322&rft.volume=14&rft.issue=1&rft_id=info:doi/10.1038%2Fs41598-024-74318-3&rft.externalDBID=n%2Fa&rft.externalDocID=10_1038_s41598_024_74318_3
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2045-2322&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2045-2322&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2045-2322&client=summon