Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell
Abstract
:1. Introduction
1.1. Gap in the Literature
1.2. Need for This Review
1.3. General Growth Requirements
1.4. Antibiotic Resistance in L. pneumophila
1.5. Relationship with Host Cells
1.6. Implications of This Study
2. Materials and Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Study Selection
3. Results
3.1. Lifecycle and Legionella Containing Vacuoles
Protein | Function | Target | Reference |
---|---|---|---|
AnkB | Translocated effector, allows proliferation of bacteria. | LCV | [47,62] |
AnkG | Prevents apoptosis of host cell allowing for continued replication of L. pneumophila in mammalian hosts. | Host protein gCq1R(p32) | [63] |
DsbA2 | Catalyzes the disulfide bond formation required for the extracytoplasmic assembly of the T4SS system of L. pneumophila. | Dot/Icm T4SS | [64] |
Dot/Icm Type 4 Secretion System (T4SS) | Translocates over 300 proteins into the host cells. Modulates host processes including phagosome-lysosome binding, promotion of ubiquitin conjugates, and suppression of dendritic cell formation. | Icm/Dot Translocated substrates (IDTS) | [65,66,67,68] |
DrrA | Required for host cytotoxicity. Recruits and activates Rab1 on the plasma membrane-derived organelles. | Host vesicular transport | [56] |
IcmSW | Mediates a conformational change facilitating T4SS recognition of the effector protein, thereby enhancing effector protein delivery | Translocation domain in the effector protein | [69] |
IcmQ | Forms pores in lipid membranes by utilizing a chaperone/substrate relationship. | [70] | |
IcmR | Binds to the N-terminal of IcmQ inhibiting membrane insertion and pore formation. | IcmQ | [70] |
LbtP | Sidephore transport protein which allows for growth in iron-limiting conditions. Prevents premature exit of macrophage due to low nutrients. | [26] | |
LbtU | Sidephore transport protein which imports iron-bound legiobactin. Alos for growth in iron-limiting conditions. | Legiobactin | [26] |
LegC3 | Inhibits SNARE and Rab GTPase dependent membrane fusion pathway | [71] | |
LegK1 | Modulates macrophage defense and inflammatory response during infection of a host cell. | NF-kB | [72] |
LegK2 | Efficient recruitment of endoplasmic reticulum markers allowing for timely intracellular replication and ER uptake of the LCV. | T4SS | [73] |
LtpD | Intracellular bacterial replication. | Phosphatidylinositol 3-phosphate | [74] |
PieA | Avoids phagososome/lysosome binding. Allows for growth in the cell. | LCV | [75,76,77] |
PI4P | Localization of effectors to LCV early during infection. | [48,78] | |
PmrA | Allows for intracellular growth in host cells. | Dot/Icm Type 4 secretion system | [79] |
RalF | Exchange factor for the ARF family of GTPase. Required for the localization of ARF of LCV | ARF | [80] |
Rap1 | Allows for intracellular bacterial replication. | [81] | |
RpkA | Localizes endosomal membranes, specifically recruited to the phagosome. | LCV | [13] |
RpoS | Stimulates intracellular replication and osmotic resistance. Growth phase stress resistance in protozoa. Maximum flagellin expression. | fliA, flaA, mip | [82,83,84] |
SidC | Involved in recruiting host ER proteins to the surface of the LCV, allowing for intracellular bacterial replication. | LCV, PtdIns(4)P | [85] |
SidF | Allows for more bacterial replication by making host cell resistant to apoptosis. | NIP3, Mcl-rambo | [86] |
SidH | Important in early phase of infection. Inhibits cells death. | [87] | |
SetA | Allows for bacterial virulence in the post-exponential growth phase by preventing entry of the LCBB into the endocytic network. | LCV | [88] |
3.2. Flagella
3.3. Interferons
3.4. Mediated Cell Death
3.5. Stress
4. Discussion
4.1. L. pneumophila in Premise Plumbing Systems
4.2. Genetic Knockdowns
4.3. Contribution to the Literature
4.4. Limitation of This Systematic Review
5. Future Directions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Function | Target | Reference |
---|---|---|---|
Dot/Icm Complex | Avoids phagososome/lysosome binding. Allows for growth in the cell and genetic conjugation. | LCV | [75,76,77,111,112] |
ankB | Intracellular replication in U937, A. polyphaga, and human monocyte-derived macrophages. | [62] | |
ccm locus | Growth, intracellular infection and virulence, especially in low iron environments | Cytochrome c | [25] |
dotA | Intracellular replication within macrophages, required in the immediate stages of infection to prevent lysozyme fusion. Not required for growth within amoeba or nematodes. | [75,113,114,115,116,117] | |
dotB | Not required for intracellular growth in amoeba. | [113] | |
dotO | Infection of A549 alveolar epithelial cells. | Activates caspase 3, 8, 9, and 1. Released HMGB1. | [118] |
katA | Bifunctional catalase-peroxidase. Keeps hydrogen peroxidase levels low in the cell allowing intracellular multiplication. | LAMP-1, recruits phagosomes | [113,119,120] |
katB | Bifunctional catalase-peroxidase. Keeps hydrogen peroxidase levels low in the cell allowing for intracellular multiplication, | LAMP-1, recruits phagosomes | [113,119,120] |
pilD | Intracellular growth in U937 and amoeba | Type II Secretion System | [53] |
rib | Expression of pore-forming toxin/activity | [121] | |
sidJ | Growth in macrophage and amoeba | [115] | |
sdjA | Growth in protozoan, but not macrophages | [115] | |
sdhA | Prevention of cell death-Mutation has increased nuclear degradation, mitochondrial distribution, membrane permeability, and caspase activation | Type I IFN expression | [110,122] |
sdeC | Efficient intracellular growth | [101] |
Gene | Host Cell | Change in Growth Rate Efficiency 1 | Degradation of Growth Rate 2 | Process |
---|---|---|---|---|
dotA | U937 | 35–56% | 35–56% | Phagosome–lysosome fusion occurs [77]. |
dotA | A. Castellanni | Incapable of replication | 100% | Phagosome–lysosome fusion occurs [150] |
dsbA | A. castellanni | ½ log reduction | 68% | Defective oxidative protein folding necessary for replication [151] |
icmQ | U937 | Incapable of replication | 100% | Defective pore formation in the macrophage [152] |
icmR | U937 | 1.5 log reduction | 97% | Defective pore formation in the macrophage [152] |
icmS | U937 | 1.75 log reduction | 98% | Phagosome–lysosome fusion occurs [152] |
icmT | U937 | Incapable of replication | 100% | Phagosome–lysosome fusion occurs [153] |
icmW | U937 | 2 log reduction | 99% | Phagosome–lysosome fusion occurs [153] |
katA | A. castellanni | 2 log reduction | 99% | Susceptible to exogenous hydrogen peroxide [113] |
katB | A. castellanni | 2 log reduction | 99% | Susceptible to exogenous hydrogen peroxide [113] |
lvgA | U937 | 10-fold decrease | 90% | Phagosome–lysosome fusion occurs [150] |
lvgA | A. castellanni | 10-fold decrease | 90% | Phagosome–lysosome fusion occurs [150] |
Gene | Host Cell | Change in Egress Rate Efficiency 1 | Degradation of Egress Rate 2 | Process |
---|---|---|---|---|
dotA | U937 | 75–85% | 75–85% | Defect in inserting pores in eukaryotic membranes [132] |
dotBCD | U937 | 80% | 80% | Defect in inserting pores in eukaryotic membranes [132] |
icmGCD | U937 | 70–75% | 70–75% | Defect in inserting pores in eukaryotic membranes [132] |
icmJB | U937 | 65–80% | 65–80% | Defect in inserting pores in eukaryotic membranes [132] |
icmT | U937 | 90% | 90% | Defect in pore-formation to egress from cell [153] |
legK2 | A. castellanni | 1.5 log reduction | 96.8% | Defect in ER recruitment on the LCV [73] |
rib | U937 | 70–95% | 70–95% | Defective in necrosis-mediated killing of the host cell [121] |
rib | WI-26 | 85–98% | 85–98% | Defective in necrosis-mediated killing of the host cell [121] |
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Mraz, A.L.; Weir, M.H. Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell. Microorganisms 2022, 10, 141. https://doi.org/10.3390/microorganisms10010141
Mraz AL, Weir MH. Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell. Microorganisms. 2022; 10(1):141. https://doi.org/10.3390/microorganisms10010141
Chicago/Turabian StyleMraz, Alexis L., and Mark H. Weir. 2022. "Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell" Microorganisms 10, no. 1: 141. https://doi.org/10.3390/microorganisms10010141
APA StyleMraz, A. L., & Weir, M. H. (2022). Knowledge to Predict Pathogens: Legionella pneumophila Lifecycle Systematic Review Part II Growth within and Egress from a Host Cell. Microorganisms, 10(1), 141. https://doi.org/10.3390/microorganisms10010141