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Published on: October 13, 2015
Endocytic mechanisms utilized by chlamydiae and their influence on induction of productive infection
1Microbial Molecular Genetics and Cell Biology Group, School of Biological Sciences, University of Birmingham, United Kingdom.
Abstract:
The microfilament-disrupting drug cytochalasin D and, initially, inoculation at 20 degrees C were used to differentiate between phagocytosis (sensitive to both treatments) and pinocytosis (resistant to both treatments) to assess whether chlamydial uptake into McCoy cells occurred by one or both mechanisms and whether each could contribute to productive infection. Both treatments suppressed the infectivity of Chlamydia trachomatis L2/434/Bu and C. psittaci GPIC (the guinea pig inclusion conjunctivitis strain) following static inoculation by only 50%, indicating that there was simultaneous operation of both phagocytosis and pinocytosis during uptake that led to productive infection. Measurement of the entry of organisms by two separate assays established that both strains predominantly used a cytochalasin D-resistant (pinocytic) mechanism, implying that phagocytic uptake was coupled to a higher frequency of productive infection. Integration of the data on infectivity and entry allowed the potential for an organism to infect a host cell to be quantified. This synthesis revealed that for both strains the infectivity potential following phagocytic entry was ca. 10-fold greater than that following pinocytic entry. However, both entry mechanisms were exploited more efficiently by strain L2/434/Bu than by strain GPIC (unless the latter was inoculated with centrifugation), indicating that intrinsic strain properties are more important for infectivity potential than the endocytic mechanism utilized.
Insights
Chlamydia trachomatis utilizes both phagocytosis and pinocytosis for host cell entry, with phagocytosis offering a tenfold greater infection potential. Strain properties significantly influence infectivity more than the entry mechanism.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Chlamydial infections are significant global health concerns.
- Understanding host cell entry mechanisms is crucial for developing effective treatments.
- Phagocytosis and pinocytosis are distinct cellular uptake processes.
Purpose of the Study:
- To determine if Chlamydia trachomatis enters McCoy cells via phagocytosis, pinocytosis, or both.
- To assess the contribution of each entry mechanism to productive infection.
- To quantify the infectivity potential associated with each entry route.
Main Methods:
- Utilized cytochalasin D (microfilament disruptor) and temperature shifts (20°C) to differentiate phagocytosis and pinocytosis.
- Measured chlamydial organism entry using two distinct assays.
- Quantified infectivity of Chlamydia trachomatis L2/434/Bu and C. psittaci GPIC strains.
Main Results:
- Both phagocytosis and pinocytosis contributed to productive infection, with approximately 50% suppression of infectivity by treatments.
- Chlamydial strains predominantly used a cytochalasin D-resistant (pinocytic) entry mechanism.
- Phagocytic entry conferred approximately tenfold greater infectivity potential compared to pinocytic entry.
- Strain L2/434/Bu exploited both entry mechanisms more efficiently than strain GPIC.
Conclusions:
- Chlamydial uptake involves simultaneous phagocytosis and pinocytosis, both leading to productive infection.
- Phagocytosis is a more efficient route for productive chlamydial infection than pinocytosis.
- Intrinsic properties of Chlamydia strains are more critical for infectivity than the specific endocytic mechanism employed.
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