COMPARATIVE ANALYSIS OF HUMAN ISOLATES OF Leptospira interrogans RESPONSIBLE OF SEVERE PULMONARY HEMMORRHAGIC SYNDROME

SIGNORELLI NUÑEZ, GEORGINA ; FARACE, PABLO DANIEL; CHIANI, YOSENA; LANDOLT, NOELIA; JACOB, PAULINA; SCHMELING, MARÍA FERNANDA; MARGENET, LETICIA; SANTANGELO, M. DE LA PAZ; CAIMI, KARINA

Congreso; XVII Congreso Argentino de Microbiología General; 2022

Leptospirosis is a reemergent zoonosis worldwide distributed caused by spirochetes of Leptospira genus. The disease span a wide range of non-specific symptoms such as fever, myalgia and headache that goes from a subclinical infection to a severe syndrome with hemorrhages and failures in different organs, mainly kidneys, which is known as Weil´s syndrome. In recent years, it has been demonstrated both locally and internationally, the increase of severe forms known as severe pulmonary hemorrhagic syndrome (SHPS), which is often clinically confused with viral pneumonitis and has a mortality rate greater than 50%. For this reason, the objective of this work was to characterize three human isolates of Leptospira interrogans that produce SHPS (YCC1, YCC2 and YCC3). The isolates were obtained from serum samples of patients belonging to the provinces of Santa Fe and Entre Ríos. In all three cases, the patients presented a proven diagnosis of Leptospirosis with a fatal outcome. Serological characterization indicates that the strains belong to serovars that generally circulate in humans, Icterohaemorrhagiae (YCC1), Pomona (YCC2) and Canicola (YCC3). Molecular typing by Multilocus Sequence Typing (MLST) indicates that the strains belong to genotypes with the majority circulation in Argentina: ST47 ST52 and ST3 respectively. These genotypes are closely related to the serogroups mentioned. On the other hand, the complete genomic sequences of the three strains were obtained. A preliminary phylogenetic analysis was performed using other human Leptospira genomes obtained from databases. The phylogenetic tree showed that YCC1 grouped with strains that caused SHPS, while YCC2 and YCC3 grouped with strains that cause mild leptospirosis. The growth rate of the strains was higher than that of the reference strain, reaching the exponential phase between 7 and 15 days of culture, while the reference strain did so from day 16. Hamster model was used to recover the virulence of the strains. The three strains presented different degrees of virulence compared to the control, so the animals were euthanized at different times post-infection. The macroscopic analysis allowed us to observe micro-hemorrhages in the lung, being able to recover one of the strains from lungs but no from urine. These results indicate that even the strains belong to serogroups and genotypes frequently found in human population in Argentina, they present a differential degree of virulence with tropism to lungs what correlate with the clinical presentation observed in patients, making it necessary to delve into the knowledge of the same in order to identify possible targets of differential diagnosis.