Incidence of an intracellular multiplication niche amongst<i>Acinetobacter baumannii</i>clinical isolates

Rubio, Tristan; Gagné, Stéphanie; Debruyne, Charline; Dias, Chloé; Cluzel, Caroline; Mongellaz, Doriane; Rousselle, Patricia; Göttig, Stephan; Seifert, Harald; Higgins, Paul G.; Salcedo, Suzana P.

doi:10.1101/2021.04.15.439986

Cited by 3 publications

(1 citation statement)

References 42 publications

(55 reference statements)

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“…During the revision of this work, the Salcedo group reported that a subset of modern clinical isolates replicates within non-autophagic ACVs in epithelial cells [29]. In agreement with our results, large ACVs containing up to 50 bacteria were visualized in multiple non-phagocytic cells.…”

Section: Plos Pathogenssupporting

confidence: 90%

Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

et al. 2021

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Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication of A. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance of A. baumannii.

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Section: Plos Pathogenssupporting

confidence: 90%

Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

et al. 2021

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Investigation of Peptidoglycan-Associated Lipoprotein of Acinetobacter baumannii and Its Interaction with Fibronectin To Find Its Therapeutic Potential

Solanki

Tiwari

2023

Infect Immun

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Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH

Distel¹,

Venanzio²,

Mackel³

et al. 2023

PLoS Pathog

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Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, but not the lab strain 19606, can infect alveolar macrophages and produce ACVs in vivo in a murine pneumonia model. Both strains initially interact with the alveolar macrophage endocytic pathway, as indicated by EEA1 and LAMP1 markers; however, the fate of these strains diverges at a later stage. While 19606 is eliminated in an autophagy pathway, 398 replicates in ACVs and are not degraded. We show that 398 reverts the natural acidification of the phagosome by secreting large amounts of ammonia, a by-product of amino acid catabolism. We propose that this ability to survive within macrophages may be critical for the persistence of clinical A. baumannii isolates in the lung during a respiratory infection.

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Incidence of an intracellular multiplication niche amongstAcinetobacter baumanniiclinical isolates

Cited by 3 publications

References 42 publications

Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

Investigation of Peptidoglycan-Associated Lipoprotein of Acinetobacter baumannii and Its Interaction with Fibronectin To Find Its Therapeutic Potential

Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH

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