PMID- 33222688
OWN - NLM
STAT- MEDLINE
DCOM- 20210902
LR  - 20210902
IS  - 1476-0711 (Electronic)
IS  - 1476-0711 (Linking)
VI  - 19
IP  - 1
DP  - 2020 Nov 22
TI  - Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium 
      abscessus: a model to study antimycobacterial agents.
PG  - 52
LID - 10.1186/s12941-020-00399-3 [doi]
LID - 52
AB  - BACKGROUND: Multidrug-resistant infections due to Mycobacterium abscessus often 
      require complex and prolonged regimens for treatment. Here, we report the 
      evaluation of a new ex vivo antimicrobial susceptibility testing model using 
      organotypic cultures of murine precision-cut lung slices, an experimental model 
      in which metabolic activity, and all the usual cell types of the organ are found 
      while the tissue architecture and the interactions between the different cells 
      are maintained. METHODS: Precision cut lung slices (PCLS) were prepared from the 
      lungs of wild type BALB/c mice using the Krumdieck((R)) tissue slicer. Lung tissue 
      slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we 
      tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 mug/mL) and 
      tigecycline (0.25, 1 and 4 mug/mL), at 12, 24 and 48 h. Afterwards, CFUs were 
      determined plating on blood agar to measure the surviving intracellular bacteria. 
      The viability of PCLS was assessed by Alamar Blue assay and corroborated using 
      histopathological analysis. RESULTS: PCLS were successfully infected with a 
      virulent strain of M. abscessus as demonstrated by CFUs and detailed 
      histopathological analysis. The time-course infection, including tissue damage, 
      parallels in vivo findings reported in genetically modified murine models for M. 
      abscessus infection. Tigecycline showed a bactericidal effect at 48 h that 
      achieved a reduction of > 4log(10) CFU/mL against the intracellular mycobacteria, 
      while imipenem showed a bacteriostatic effect. CONCLUSIONS: The use of this new 
      organotypic ex vivo model provides the opportunity to test new drugs against M. 
      abscessus, decreasing the use of costly and tedious animal models.
FAU - Molina-Torres, Carmen Amelia
AU  - Molina-Torres CA
AD  - Servicio de Dermatologia, Hospital Universitario "Jose E. Gonzalez", Universidad 
      Autonoma de Nuevo Leon, Monterrey, NL, Mexico.
FAU - Flores-Castillo, Oscar Noe
AU  - Flores-Castillo ON
AD  - Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, 
      NL, Mexico.
FAU - Carranza-Torres, Irma Edith
AU  - Carranza-Torres IE
AD  - Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, 
      NL, Mexico.
AD  - Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro 
      Social, Monterrey, NL, Mexico.
FAU - Guzman-Delgado, Nancy Elena
AU  - Guzman-Delgado NE
AD  - Division de Investigacion en Salud, UMAE, Hospital de Cardiologia #34, Instituto 
      Mexicano del Seguro Social, Monterrey, NL, Mexico.
FAU - Viveros-Valdez, Ezequiel
AU  - Viveros-Valdez E
AD  - Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, 
      NL, Mexico.
FAU - Vera-Cabrera, Lucio
AU  - Vera-Cabrera L
AD  - Servicio de Dermatologia, Hospital Universitario "Jose E. Gonzalez", Universidad 
      Autonoma de Nuevo Leon, Monterrey, NL, Mexico.
FAU - Ocampo-Candiani, Jorge
AU  - Ocampo-Candiani J
AD  - Servicio de Dermatologia, Hospital Universitario "Jose E. Gonzalez", Universidad 
      Autonoma de Nuevo Leon, Monterrey, NL, Mexico.
FAU - Verde-Star, Julia
AU  - Verde-Star J
AD  - Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, 
      NL, Mexico.
FAU - Castro-Garza, Jorge
AU  - Castro-Garza J
AD  - Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro 
      Social, Monterrey, NL, Mexico.
FAU - Carranza-Rosales, Pilar
AU  - Carranza-Rosales P
AUID- ORCID: 0000-0002-8944-9298
AD  - Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro 
      Social, Monterrey, NL, Mexico. carranza60@yahoo.com.mx.
LA  - eng
PT  - Journal Article
DEP - 20201122
PL  - England
TA  - Ann Clin Microbiol Antimicrob
JT  - Annals of clinical microbiology and antimicrobials
JID - 101152152
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*administration & dosage
MH  - Humans
MH  - In Vitro Techniques
MH  - Lung/*microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Models, Biological
MH  - Mycobacterium Infections, Nontuberculous/*drug therapy/microbiology
MH  - Mycobacterium abscessus/*drug effects/physiology
PMC - PMC7680588
OTO - NOTNLM
OT  - Ex vivo infection
OT  - Lung tissue slices
OT  - Mycobacterium abscessus
COIS- The authors declare that they have no competing interests.
EDAT- 2020/11/24 06:00
MHDA- 2021/09/03 06:00
PMCR- 2020/11/22
CRDT- 2020/11/23 05:23
PHST- 2019/12/22 00:00 [received]
PHST- 2020/11/12 00:00 [accepted]
PHST- 2020/11/23 05:23 [entrez]
PHST- 2020/11/24 06:00 [pubmed]
PHST- 2021/09/03 06:00 [medline]
PHST- 2020/11/22 00:00 [pmc-release]
AID - 10.1186/s12941-020-00399-3 [pii]
AID - 399 [pii]
AID - 10.1186/s12941-020-00399-3 [doi]
PST - epublish
SO  - Ann Clin Microbiol Antimicrob. 2020 Nov 22;19(1):52. doi: 
      10.1186/s12941-020-00399-3.