scholarly journals Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system

Microbiology ◽  
2017 ◽  
Vol 163 (10) ◽  
pp. 1436-1444 ◽  
Author(s):  
Charlton Lam ◽  
Melissa Jamerson ◽  
Guy Cabral ◽  
Ana Maris Carlesso ◽  
Francine Marciano-Cabral
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Matrix Metalloproteinases ◽  
Naegleria Fowleri ◽  
The Central Nervous System ◽  
Nægleria Fowleri

scholarly journals Seasonal Meningoencephalitis in Holstein Cattle Caused by Naegleria Fowleri

2005 ◽  
Vol 17 (6) ◽  
pp. 605-609 ◽  
Author(s):  
Barbara M. Daft ◽  
Govinda S. Visvesvara ◽  
Deryck H. Read ◽  
Hailu Kinde ◽  
Francisco A. Uzal ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drinking Water ◽  
Central Nervous System Disease ◽  
Nervous System Disease ◽  
Holstein Cattle ◽  
Naegleria Fowleri ◽  
System Disease ◽  
Nægleria Fowleri ◽  
Amoebic Meningoencephalitis

Primary amoebic meningoencephalitis is a fulminant infection of the human central nervous system caused by Naegleria fowleri, a free-living amoeba that thrives in artificially or naturally heated water. The infection usually is acquired while bathing or swimming in such waters. The portal of entry is the olfactory neuroepithelium. This report describes fatal meningoencephalitis caused by N. fowleri in Holstein cattle that consumed untreated surface water in an area of California where summer temperatures at times exceed 42°C. In the summers of 1998 and 1999, severe multifocal necrosuppurative hemorrhagic meningoencephalitis was observed in brain samples from nine 10-20-month-old heifers with clinical histories of acute central nervous system disease. Olfactory lobes and cerebella were most severely affected. Lesions were also evident in periventricular and submeningeal neuropil as well as olfactory nerves. Naegleria fowleri was demonstrated by immunohistochemistry in brain and olfactory nerve lesions and was isolated from one brain. Even though cultures of drinking water did not yield N. fowleri, drinking water was the likely source of the amoeba. The disease in cattle closely resembles primary amoebic meningoencephalitis in humans. Naegleria meningoencephalitis should be included among differential diagnoses of central nervous system disease in cattle during the summer season in areas with high ambient temperatures.

scholarly journals Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens

2015 ◽  
Vol 59 (4) ◽  
pp. 2037-2044 ◽  
Author(s):  
Christopher A. Rice ◽  
Beatrice L. Colon ◽  
Mehmet Alp ◽  
Hakan Göker ◽  
David W. Boykin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Throughput ◽  
Lead Optimization ◽  
New Drugs ◽  
Naegleria Fowleri ◽  
Onset Of Action ◽  
Content Type ◽  
Nægleria Fowleri

ABSTRACTNaegleria fowleriis a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two newin vitroassays suitable for medium- or high-throughput drug discovery and used these forN. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections withN. fowleri.

scholarly journals The Activity of Matrix Metalloproteinases (MMP-2, MMP-9) and Their Tissue Inhibitors (TIMP-1, TIMP- 3) in the Cerebral Cortex and Hippocampus in Experimental Acanthamoebiasis

2018 ◽  
Vol 19 (12) ◽  
pp. 4128 ◽  
Author(s):  
Natalia Łanocha-Arendarczyk ◽  
Irena Baranowska-Bosiacka ◽  
Izabela Gutowska ◽  
Agnieszka Kolasa-Wołosiuk ◽  
Karolina Kot ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Matrix Metalloproteinases ◽  
Defense Mechanism ◽  
Pathological Process ◽  
Tissue Inhibitors ◽  
Immunological Status ◽  
The Central Nervous System ◽  
Increased Activity

The pathological process occurring within the central nervous system (CNS) as a result of the infection by Acanthamoeba spp. is not fully understood. Therefore, the aim of this study was to determine whether Acanthamoeba spp. may affect the levels of matrix metalloproteinases (MMP-2,- 9), their tissue inhibitors (TIMP-1,-3) and MMP-9/TIMP-1, MMP-2/TIMP-3 ratios in the cerebral cortex and hippocampus, in relation to the host’s immunological status. Our results showed that Acanthamoeba spp. infection can change the levels of MMP and TIMP in the CNS and may be amenable targets for limiting amoebic encephalitis. The increase in the activity of matrix metalloproteinases during acanthamoebiasis may be primarily the result of inflammation process, probably an increased activity of proteolytic processes, but also (to a lesser extent) a defense mechanism preventing the processes of neurodegeneration.

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