scholarly journals Density-dependent resistance protectsLegionella pneumophilafrom its own antimicrobial metabolite, HGA

2018 ◽  
Author(s):  
Tera C. Levin ◽  
Brian P. Goldspiel ◽  
Harmit S. Malik
Keyword(s):  
Legionella Pneumophila ◽  
Bacterial Pathogen ◽  
Stringent Response ◽  
Density Dependent ◽  
Redox Active ◽  
Self Harm ◽  
Antimicrobial Metabolite ◽  
Isogenic Strains ◽  
Toxic Molecule ◽  
Active Precursor

AbstractTo persist in the extracellular state, the bacterial pathogenLegionella pneumophilamust withstand competition from neighboring bacteria. Here, we find thatL. pneumophilacan antagonize the growth of neighboringLegionellaspecies using a secreted inhibitor: HGA (homogentisic acid), the unstable, redox-active precursor molecule toL. pneumophila’s brown-black pigment. Unexpectedly, we find thatL. pneumophilacan itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identifylpg1681as a gene that modulatesL. pneumophilasusceptibility to HGA. We find thatL. pneumophilasensitivity to HGA is density-dependent and cell intrinsic. This resistance is not mediated by the stringent response nor the previously describedLegionellaquorum-sensing pathway. Instead, we find thatL. pneumophilacells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We speculate that establishedLegionellacommunities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.

scholarly journals Density-dependent resistance protects Legionella pneumophila from its own antimicrobial metabolite, HGA

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tera C Levin ◽  
Brian P Goldspiel ◽  
Harmit S Malik
Keyword(s):  
Legionella Pneumophila ◽  
Bacterial Pathogen ◽  
Stringent Response ◽  
Intrinsic Resistance ◽  
Density Dependent ◽  
Legionella Species ◽  
Self Harm ◽  
Antimicrobial Metabolite ◽  
Isogenic Strains ◽  
Toxic Molecule

To persist in microbial communities, the bacterial pathogen Legionella pneumophila must withstand competition from neighboring bacteria. Here, we find that L. pneumophila can antagonize the growth of other Legionella species using a secreted inhibitor: HGA (homogentisic acid). Unexpectedly, L. pneumophila can itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identify lpg1681 as a gene that modulates L. pneumophila susceptibility to HGA. We find that L. pneumophila sensitivity to HGA is density-dependent and cell intrinsic. Resistance is not mediated by the stringent response nor the previously described Legionella quorum-sensing pathway. Instead, L. pneumophila cells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We propose that established Legionella communities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.

scholarly journals Atypical Bacterial Pathogens and Small-Vessel Leukocytoclastic Vasculitis of the Skin in Children: Systematic Literature Review

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
Céline Betti ◽  
Pietro Camozzi ◽  
Viola Gennaro ◽  
Mario G. Bianchetti ◽  
Martin Scoglio ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Legionella Pneumophila ◽  
Leukocytoclastic Vasculitis ◽  
Systemic Vasculitis ◽  
Bacterial Pathogen ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
Systemic Involvement ◽  
Symptomatic Disease ◽  
Atypical Pathogen

Leukocytoclastic small-vessel vasculitis of the skin (with or without systemic involvement) is often preceded by infections such as common cold, tonsillopharyngitis, or otitis media. Our purpose was to document pediatric (≤18 years) cases preceded by a symptomatic disease caused by an atypical bacterial pathogen. We performed a literature search following the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. We retained 19 reports including 22 cases (13 females and 9 males, 1.0 to 17, median 6.3 years of age) associated with a Mycoplasma pneumoniae infection. We did not find any case linked to Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella pneumophila. Patients with a systemic vasculitis (N = 14) and with a skin-limited (N = 8) vasculitis did not significantly differ with respect to gender and age. The time to recovery was ≤12 weeks in all patients with this information. In conclusion, a cutaneous small-vessel vasculitis with or without systemic involvement may occur in childhood after an infection caused by the atypical bacterial pathogen Mycoplasma pneumoniae. The clinical picture and the course of cases preceded by recognized triggers and by this atypical pathogen are indistinguishable.

scholarly journals Stringent Response Activates Quorum Sensing and Modulates Cell Density-Dependent Gene Expression inPseudomonas aeruginosa

2001 ◽  
Vol 183 (18) ◽  
pp. 5376-5384 ◽  
Author(s):  
Christian van Delden ◽  
Rachel Comte ◽  
And Marc Bally
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Cell Density ◽  
Stringent Response ◽  
Transcriptional Regulators ◽  
Homoserine Lactone ◽  
Density Dependent ◽  
Sensing Systems ◽  
Acid Analogue ◽  
Enhanced Expression

ABSTRACT During nutrient starvation, Escherichia coli elicits a stringent response involving the ribosome-associated protein RelA. Activation of RelA results in a global change in the cellular metabolism including enhanced expression of the stationary-phase sigma factor RpoS. In the human pathogen Pseudomonas aeruginosa, a complex quorum-sensing circuitry, linked to RpoS expression, is required for cell density-dependent production of many secreted virulence factors, including LasB elastase. Quorum sensing relies on the activation of specific transcriptional regulators (LasR and RhlR) by their corresponding autoinducers (3-oxo-C12-homoserine lactone [HSL] and C4-HSL), which function as intercellular signals. We found that overexpression of relA activated the expression of rpoS in P. aeruginosa and led to premature, cell density-independent LasB elastase production. We therefore investigated the effects of the stringent response on quorum sensing. Both lasR and rhlR gene expression and autoinducer synthesis were prematurely activated during the stringent response induced by overexpression of relA. Premature expression of lasR and rhlR was also observed when relA was overexpressed in a PAO1 rpoSmutant. The stringent response induced by the amino acid analogue serine hydroxamate (SHX) also led to premature production of the 3-oxo-C12-HSL autoinducer. This response to SHX was absent in a PAO1 relA mutant. These findings suggest that the stringent response can activate the two quorum-sensing systems of P. aeruginosa independently of cell density.

ThehtpABoperon ofLegionella pneumophilacannot be deleted in the presence of thegroEchaperonin operon ofEscherichia coli

2011 ◽  
Vol 57 (11) ◽  
pp. 943-952 ◽  
Author(s):  
Gheyath K. Nasrallah ◽  
Elizabeth Gagnon ◽  
Dennis J. Orton ◽  
Rafael A. Garduño
Keyword(s):  
Southern Blot ◽  
Legionella Pneumophila ◽  
Bacterial Pathogen ◽  
Phenotypic Selection ◽  
Correct Selection ◽  
Pcr Analysis ◽  
Allelic Replacement ◽  
Gentamicin Resistance

HtpB, the chaperonin of the intracellular bacterial pathogen Legionella pneumophila , displays several virulence-related functions in vitro. To confirm HtpB’s role in vivo, host infections with an htpB deletion mutant would be required. However, we previously reported that the htpAB operon (encoding co-chaperonin and chaperonin) is essential. We attempted here to delete htpAB in a L. pneumophila strain carrying the groE operon (encoding the Escherichia coli co-chaperonin and chaperonin). The groE operon was inserted into the chromosome of L. pneumophila Lp02, and then allelic replacement of htpAB with a gentamicin resistance cassette was attempted. Although numerous potential postallelic replacement transformants showed a correct selection phenotype, we still detected htpAB by PCR and full-size HtpB by immunoblot. Southern blot and PCR analysis indicated that the gentamicin resistance cassette had apparently integrated in a duplicated htpAB region. However, we showed by Southern blot that strain Lp02, and the Lp02 derivative carrying the groE operon, have only one copy of htpAB. These results confirmed that the htpAB operon cannot be deleted, not even in the presence of the groE operon, and suggested that attempts to delete htpAB under strong phenotypic selection result in aberrant genetic recombinations that could involve duplication of the htpAB locus.

scholarly journals Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors

2021 ◽  
Vol 4 (12) ◽  
pp. e202101247
Author(s):  
Nnejiuwa U Ibe ◽  
Advait Subramanian ◽  
Shaeri Mukherjee
Keyword(s):  
Legionella Pneumophila ◽  
Nuclear Translocation ◽  
Bacterial Pathogen ◽  
Effector Proteins ◽  
Regulatory Control ◽  
Unfolded Protein ◽  
Bacterial Proteins ◽  
Protein Response ◽  
Upr Pathway ◽  
Target Gene Transcription

The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this L.p.–dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.

scholarly journals The Dot/Icm Type IV Secretion System of Legionella pneumophila Is Essential for the Induction of Apoptosis in Human Macrophages

2002 ◽  
Vol 70 (3) ◽  
pp. 1657-1663 ◽  
Author(s):  
Steven D. Zink ◽  
Lisa Pedersen ◽  
Nicholas P. Cianciotto ◽  
Yousef Abu Kwaik
Keyword(s):  
Legionella Pneumophila ◽  
Mammalian Cells ◽  
Bacterial Pathogen ◽  
Secretion System ◽  
Type Iv Secretion ◽  
Type Iv Secretion System ◽  
Type Ii Secretion ◽  
Type Iv ◽  
Induction Of Apoptosis

ABSTRACT We have previously shown that Legionella pneumophila induces caspase 3-dependent apoptosis in mammalian cells during early stages of infection. In this report, we show that nine L. pneumophila strains with mutations in the dotA, dotDCB, icmT, icmGCD, and icmJB loci are completely defective in the induction of apoptosis, in addition to their severe defects in intracellular replication and pore formation-mediated cytotoxicity. Importantly, all nine dot/icm mutants were complemented for all their defective phenotypes with the respective wild-type loci. We show that the role of the Dot/Icm type IV secretion system in the induction of apoptosis is independent of the RtxA toxin, the dot/icm-regulated pore-forming toxin, and the type II secretion system. However, the pore-forming toxin, which is triggered upon entry into the postexponential growth phase, enhances the ability of L. pneumophila to induce apoptosis. Our data provide the first example of the role of a type IV secretion system of a bacterial pathogen in the induction of apoptosis in the host cell.

scholarly journals Legionella Subvert the Functions of Rab1 and Sec22b to Create a Replicative Organelle

2004 ◽  
Vol 199 (9) ◽  
pp. 1201-1211 ◽  
Author(s):  
Jonathan C. Kagan ◽  
Mary-Pat Stein ◽  
Marc Pypaert ◽  
Craig R. Roy
Keyword(s):  
Endoplasmic Reticulum ◽  
Legionella Pneumophila ◽  
Molecular Mechanisms ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Intracellular Growth ◽  
Host Proteins ◽  
Morphological Studies ◽  
Bacterial Replication ◽  
Inhibition Studies

Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside a specialized organelle that is morphologically similar to the endoplasmic reticulum (ER). To better understand the molecular mechanisms governing transport of the Legionella-containing vacuole (LCV), we have identified host proteins that participate in the conversion of the LCV into a replicative organelle. Our data show that Rab1 is recruited to the LCV within minutes of uptake. Rab1 recruitment to the LCV precedes remodeling of this compartment by ER-derived vesicles. Genetic inhibition studies demonstrate that Rab1 is important for the recruitment of ER-derived vesicles to the LCV and that inhibiting Rab1 function abrogates intracellular growth of Legionella. Morphological studies indicate that the Sec22b protein is located on ER-derived vesicles recruited to the LCV and that Sec22b is delivered to the LCV membrane. Sec22b function was found to be important for biogenesis of the specialized organelle that supports Legionella replication. These studies demonstrate that Legionella has the ability to subvert Rab1 and Sec22b function to facilitate the transport and fusion of ER-derived vesicles with the LCV, resulting in the formation of a specialized organelle that can support bacterial replication.

scholarly journals Legionella pneumophila inhibits acidification of its phagosome in human monocytes.

1984 ◽  
Vol 99 (6) ◽  
pp. 1936-1943 ◽  
Author(s):  
M A Horwitz ◽  
F R Maxfield
Keyword(s):  
Legionella Pneumophila ◽  
Sheep Erythrocyte ◽  
Bacterial Pathogen ◽  
Human Monocytes ◽  
E Coli ◽  
The Mean ◽  
Intracellular Multiplication ◽  
Fluorescence Images ◽  
Activated Monocytes ◽  
Quantitative Fluorescence

We used quantitative fluorescence microscopy to measure the pH of phagosomes in human monocytes that contain virulent Legionella pneumophila, a bacterial pathogen that multiplies intracellularly in these phagocytes. The mean pH of phagosomes that contain live L. pneumophila was 6.1 in 14 experiments. In the same experiments, the mean pH of phagosomes containing dead L. pneumophila averaged 0.8 pH units lower than the mean pH of phagosomes containing live L. pneumophila, a difference that was highly significant (P less than 0.01 in all 14 experiments). In contrast, the mean pH of phagosomes initially containing live E. coli, which were then killed by monocytes, was the same as for phagosomes initially containing dead E. coli. The mean pH of L. pneumophila phagosomes in activated monocytes, which inhibit L. pneumophila intracellular multiplication, was the same as in nonactivated monocytes. To simultaneously measure the pH of different phagosomes within the same monocyte, we digitized and analyzed fluorescence images of monocytes that contained both live L. pneumophila and sheep erythrocytes. Within the same monocyte, live L. pneumophila phagosomes had a pH of approximately 6.1 and sheep erythrocyte phagosomes had a pH of approximately 5.0 or below. This study demonstrates that L. pneumophila is capable of modifying the pH of its phagocytic vacuole. This capability may be critical to the intracellular survival and multiplication of this and other intracellular pathogens.

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