Maria Laura Ferrando
Researcher
Area of interest:
One of my primary research interests is exploring how bacteria influence the host’s health status. This passion led me to earn a PhD in molecular microbiology and pursue a career focused on host-microbe interactions, during which I gained strong credentials in microbial genomics and clinical microbiology.
I spent 16 years abroad conducting research in the Netherlands. At Wageningen University, I utilize pipelines to analyze microbiota composition in pigs and its changes following intervention studies. Additionally, at the Academic Medical Center of Amsterdam, I extensively studied the mechanisms of virulence in zoonotic bacteria.
In 2022, I returned to Italy through the “Rientro dei Cervelli” program and joined the San Raffaele Research Institute in Milan as researcher. Here, I worked on various projects focused on “Antimicrobial Resistance” in nosocomial bacterial pathogens using NGS-based methods.
Recently, I joined Dr. Sanna’s group to investigate the impact of intestinal and vaginal microbiota on the onset of cardio-metabolic diseases in women.
Most significant publications:
2024
Sterzi, Lodovico; Nodari, Riccardo; Marco, Federico Di; Ferrando, Maria Laura; Saluzzo, Francesca; Spitaleri, Andrea; Allahverdi, Hamed; Papaleo, Stella; Panelli, Simona; Rimoldi, Sara Giordana; Biffignandi, Gherard Batisti; Corbella, Marta; Cavallero, Annalisa; Prati, Paola; Farina, Claudio; Cirillo, Daniela Maria; Zuccotti, Gianvincenzo; Bandi, Claudio; Comandatore, Francesco
Genetic barriers more than environmental associations explain Serratia marcescens population structure Journal Article
In: Commun. Biol., 7 (1), pp. 468, 2024.
@article{Sterzi2024-xo,
title = {Genetic barriers more than environmental associations explain
Serratia marcescens population structure},
author = {Lodovico Sterzi and Riccardo Nodari and Federico Di Marco and Maria Laura Ferrando and Francesca Saluzzo and Andrea Spitaleri and Hamed Allahverdi and Stella Papaleo and Simona Panelli and Sara Giordana Rimoldi and Gherard Batisti Biffignandi and Marta Corbella and Annalisa Cavallero and Paola Prati and Claudio Farina and Daniela Maria Cirillo and Gianvincenzo Zuccotti and Claudio Bandi and Francesco Comandatore},
year = {2024},
date = {2024-04-01},
journal = {Commun. Biol.},
volume = {7},
number = {1},
pages = {468},
abstract = {Bacterial species often comprise well-separated lineages, likely
emerged and maintained by genetic isolation and/or ecological
divergence. How these two evolutionary actors interact in the
shaping of bacterial population structure is currently not fully
understood. In this study, we investigate the genetic and
ecological drivers underlying the evolution of Serratia
marcescens, an opportunistic pathogen with high genomic
flexibility and able to colonise diverse environments.
Comparative genomic analyses reveal a population structure
composed of five deeply-demarcated genetic clusters with open
pan-genome but limited inter-cluster gene flow, partially
explained by Restriction-Modification (R-M) systems
incompatibility. Furthermore, a large-scale research on
hundred-thousands metagenomic datasets reveals only a partial
habitat separation of the clusters. Globally, two clusters only
show a separate gene composition coherent with ecological
adaptations. These results suggest that genetic isolation has
preceded ecological adaptations in the shaping of the species
diversity, an evolutionary scenario coherent with the
Evolutionary Extended Synthesis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bacterial species often comprise well-separated lineages, likely
emerged and maintained by genetic isolation and/or ecological
divergence. How these two evolutionary actors interact in the
shaping of bacterial population structure is currently not fully
understood. In this study, we investigate the genetic and
ecological drivers underlying the evolution of Serratia
marcescens, an opportunistic pathogen with high genomic
flexibility and able to colonise diverse environments.
Comparative genomic analyses reveal a population structure
composed of five deeply-demarcated genetic clusters with open
pan-genome but limited inter-cluster gene flow, partially
explained by Restriction-Modification (R-M) systems
incompatibility. Furthermore, a large-scale research on
hundred-thousands metagenomic datasets reveals only a partial
habitat separation of the clusters. Globally, two clusters only
show a separate gene composition coherent with ecological
adaptations. These results suggest that genetic isolation has
preceded ecological adaptations in the shaping of the species
diversity, an evolutionary scenario coherent with the
Evolutionary Extended Synthesis.
emerged and maintained by genetic isolation and/or ecological
divergence. How these two evolutionary actors interact in the
shaping of bacterial population structure is currently not fully
understood. In this study, we investigate the genetic and
ecological drivers underlying the evolution of Serratia
marcescens, an opportunistic pathogen with high genomic
flexibility and able to colonise diverse environments.
Comparative genomic analyses reveal a population structure
composed of five deeply-demarcated genetic clusters with open
pan-genome but limited inter-cluster gene flow, partially
explained by Restriction-Modification (R-M) systems
incompatibility. Furthermore, a large-scale research on
hundred-thousands metagenomic datasets reveals only a partial
habitat separation of the clusters. Globally, two clusters only
show a separate gene composition coherent with ecological
adaptations. These results suggest that genetic isolation has
preceded ecological adaptations in the shaping of the species
diversity, an evolutionary scenario coherent with the
Evolutionary Extended Synthesis.
2023
Gussak, Alex; Ferrando, Maria Laura; Schrama, Mels; Baarlen, Peter; Wells, Jerry Mark
Precision genome engineering in streptococcus suis based on a broad-host-range vector and CRISPR-Cas9 technology Journal Article
In: ÄCS Synth. Biol.", 12 (9), pp. 2546–2560, 2023.
@article{Gussak2023-rj,
title = {Precision genome engineering in streptococcus suis based on a
broad-host-range vector and CRISPR-Cas9 technology},
author = {Alex Gussak and Maria Laura Ferrando and Mels Schrama and Peter Baarlen and Jerry Mark Wells},
year = {2023},
date = {2023-09-01},
journal = {ÄCS Synth. Biol."},
volume = {12},
number = {9},
pages = {2546--2560},
abstract = {Streptococcussuis is an important zoonotic pathogen that causes
severe invasive disease in pigs and humans. Current methods for
genome engineering of S. suis rely on the insertion of antibiotic
resistance markers, which is time-consuming and labor-intensive
and does not allow the precise introduction of small genomic
mutations. Here we developed a system for CRISPR-based genome
editing in S. suis, utilizing linear DNA fragments for homologous
recombination (HR) and a plasmid-based negative selection system
for bacteria not edited by HR. To enable the use of this system
in other bacteria, we engineered a broad-host-range replicon in
the CRISPR plasmid. We demonstrated the utility of this system to
rapidly introduce multiple gene deletions in successive rounds of
genome editing and to make precise nucleotide changes in
essential genes. Furthermore, we characterized a mechanism by
which S. suis can escape killing by a targeted Cas9-sgRNA complex
in the absence of HR. A characteristic of this new mechanism is
the presence of very slow-growing colonies in a persister-like
state that may allow for DNA repair or the introduction of
mutations, alleviating Cas9 pressure. This does not impact the
utility of CRISPR-based genome editing because the escape
colonies are easily distinguished from genetically edited clones
due to their small colony size. Our CRISPR-based editing system
is a valuable addition to the genetic toolbox for engineering of
S. suis, as it accelerates the process of mutant construction and
simplifies the removal of antibiotic markers between successive
rounds of genome editing.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Streptococcussuis is an important zoonotic pathogen that causes
severe invasive disease in pigs and humans. Current methods for
genome engineering of S. suis rely on the insertion of antibiotic
resistance markers, which is time-consuming and labor-intensive
and does not allow the precise introduction of small genomic
mutations. Here we developed a system for CRISPR-based genome
editing in S. suis, utilizing linear DNA fragments for homologous
recombination (HR) and a plasmid-based negative selection system
for bacteria not edited by HR. To enable the use of this system
in other bacteria, we engineered a broad-host-range replicon in
the CRISPR plasmid. We demonstrated the utility of this system to
rapidly introduce multiple gene deletions in successive rounds of
genome editing and to make precise nucleotide changes in
essential genes. Furthermore, we characterized a mechanism by
which S. suis can escape killing by a targeted Cas9-sgRNA complex
in the absence of HR. A characteristic of this new mechanism is
the presence of very slow-growing colonies in a persister-like
state that may allow for DNA repair or the introduction of
mutations, alleviating Cas9 pressure. This does not impact the
utility of CRISPR-based genome editing because the escape
colonies are easily distinguished from genetically edited clones
due to their small colony size. Our CRISPR-based editing system
is a valuable addition to the genetic toolbox for engineering of
S. suis, as it accelerates the process of mutant construction and
simplifies the removal of antibiotic markers between successive
rounds of genome editing.
severe invasive disease in pigs and humans. Current methods for
genome engineering of S. suis rely on the insertion of antibiotic
resistance markers, which is time-consuming and labor-intensive
and does not allow the precise introduction of small genomic
mutations. Here we developed a system for CRISPR-based genome
editing in S. suis, utilizing linear DNA fragments for homologous
recombination (HR) and a plasmid-based negative selection system
for bacteria not edited by HR. To enable the use of this system
in other bacteria, we engineered a broad-host-range replicon in
the CRISPR plasmid. We demonstrated the utility of this system to
rapidly introduce multiple gene deletions in successive rounds of
genome editing and to make precise nucleotide changes in
essential genes. Furthermore, we characterized a mechanism by
which S. suis can escape killing by a targeted Cas9-sgRNA complex
in the absence of HR. A characteristic of this new mechanism is
the presence of very slow-growing colonies in a persister-like
state that may allow for DNA repair or the introduction of
mutations, alleviating Cas9 pressure. This does not impact the
utility of CRISPR-based genome editing because the escape
colonies are easily distinguished from genetically edited clones
due to their small colony size. Our CRISPR-based editing system
is a valuable addition to the genetic toolbox for engineering of
S. suis, as it accelerates the process of mutant construction and
simplifies the removal of antibiotic markers between successive
rounds of genome editing.
2021
Ferrando, Maria Laura; Gussak, Alex; Mentink, Saskia; Gutierrez, Marcela Fernandez; Baarlen, Peter; Wells, Jerry Mark
Active human and porcine serum induce competence for genetic transformation in the emerging zoonotic pathogen Streptococcus suis Journal Article
In: Pathogens, 10 (2), pp. 156, 2021.
@article{Ferrando2021-ga,
title = {Active human and porcine serum induce competence for genetic transformation in the emerging zoonotic pathogen Streptococcus suis},
author = {Maria Laura Ferrando and Alex Gussak and Saskia Mentink and Marcela Fernandez Gutierrez and Peter Baarlen and Jerry Mark Wells},
year = {2021},
date = {2021-02-01},
urldate = {2021-02-01},
journal = {Pathogens},
volume = {10},
number = {2},
pages = {156},
publisher = {MDPI AG},
abstract = {The acquisition of novel genetic traits through natural
competence is a strategy used by bacteria in microbe-rich
environments where microbial competition, antibiotics, and host
immune defenses threaten their survival. Here, we show that
virulent strains of Streptococcus suis, an important zoonotic
agent and porcine pathogen, become competent for genetic
transformation with plasmid or linear DNA when cultured in
active porcine and human serum. Competence was not induced in
active fetal bovine serum, which contains less complement
factors and immunoglobulins than adult serum and was strongly
reduced in heat-treated or low-molecular weight fractions of
active porcine serum. Late competence genes, encoding the uptake
machinery for environmental DNA, were upregulated in the active
serum. Competence development was independent of the early
competence regulatory switch involving XIP and ComR, as well as
sigma factor ComX, suggesting the presence of an alternative
stress-induced pathway for regulation of the late competence
genes required for DNA uptake.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The acquisition of novel genetic traits through natural
competence is a strategy used by bacteria in microbe-rich
environments where microbial competition, antibiotics, and host
immune defenses threaten their survival. Here, we show that
virulent strains of Streptococcus suis, an important zoonotic
agent and porcine pathogen, become competent for genetic
transformation with plasmid or linear DNA when cultured in
active porcine and human serum. Competence was not induced in
active fetal bovine serum, which contains less complement
factors and immunoglobulins than adult serum and was strongly
reduced in heat-treated or low-molecular weight fractions of
active porcine serum. Late competence genes, encoding the uptake
machinery for environmental DNA, were upregulated in the active
serum. Competence development was independent of the early
competence regulatory switch involving XIP and ComR, as well as
sigma factor ComX, suggesting the presence of an alternative
stress-induced pathway for regulation of the late competence
genes required for DNA uptake.
competence is a strategy used by bacteria in microbe-rich
environments where microbial competition, antibiotics, and host
immune defenses threaten their survival. Here, we show that
virulent strains of Streptococcus suis, an important zoonotic
agent and porcine pathogen, become competent for genetic
transformation with plasmid or linear DNA when cultured in
active porcine and human serum. Competence was not induced in
active fetal bovine serum, which contains less complement
factors and immunoglobulins than adult serum and was strongly
reduced in heat-treated or low-molecular weight fractions of
active porcine serum. Late competence genes, encoding the uptake
machinery for environmental DNA, were upregulated in the active
serum. Competence development was independent of the early
competence regulatory switch involving XIP and ComR, as well as
sigma factor ComX, suggesting the presence of an alternative
stress-induced pathway for regulation of the late competence
genes required for DNA uptake.
2016
Ferrando, Maria Laura; Schultsz, Constance
A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract Journal Article
In: Gut Microbes, 7 (2), pp. 154–162, 2016.
@article{Ferrando2016-kp,
title = {A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract},
author = {Maria Laura Ferrando and Constance Schultsz},
year = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Gut Microbes},
volume = {7},
number = {2},
pages = {154--162},
publisher = {Informa UK Limited},
abstract = {Streptococcus suis (SS) is a zoonotic pathogen that can cause
systemic infection in pigs and humans. The ingestion of
contaminated pig meat is a well-established risk factor for
zoonotic S. suis disease. In our studies, we provide
experimental evidence that S. suis is capable to translocate
across the host gastro-intestinal tract (GIT) using in vivo and
in vitro models. Hence, S. suis should be considered an emerging
foodborne pathogen. In this addendum, we give an overview of the
complex interactions between S. suis and host-intestinal mucosa
which depends on the host origin, the serotype and genotype of
S. suis, as well as the presence and expression of virulence
factors involved in host-pathogen interaction. Finally, we
propose a hypothetical model of S. suis interaction with the
host-GIT taking in account differences in conditions between the
porcine and human host.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Streptococcus suis (SS) is a zoonotic pathogen that can cause
systemic infection in pigs and humans. The ingestion of
contaminated pig meat is a well-established risk factor for
zoonotic S. suis disease. In our studies, we provide
experimental evidence that S. suis is capable to translocate
across the host gastro-intestinal tract (GIT) using in vivo and
in vitro models. Hence, S. suis should be considered an emerging
foodborne pathogen. In this addendum, we give an overview of the
complex interactions between S. suis and host-intestinal mucosa
which depends on the host origin, the serotype and genotype of
S. suis, as well as the presence and expression of virulence
factors involved in host-pathogen interaction. Finally, we
propose a hypothetical model of S. suis interaction with the
host-GIT taking in account differences in conditions between the
porcine and human host.
systemic infection in pigs and humans. The ingestion of
contaminated pig meat is a well-established risk factor for
zoonotic S. suis disease. In our studies, we provide
experimental evidence that S. suis is capable to translocate
across the host gastro-intestinal tract (GIT) using in vivo and
in vitro models. Hence, S. suis should be considered an emerging
foodborne pathogen. In this addendum, we give an overview of the
complex interactions between S. suis and host-intestinal mucosa
which depends on the host origin, the serotype and genotype of
S. suis, as well as the presence and expression of virulence
factors involved in host-pathogen interaction. Finally, we
propose a hypothetical model of S. suis interaction with the
host-GIT taking in account differences in conditions between the
porcine and human host.
2015
Ferrando, Maria Laura; Greeff, Astrid; Rooijen, Willemien J M; Stockhofe-Zurwieden, Norbert; Nielsen, Jens; Schreur, Paul J Wichgers; Pannekoek, Yvonne; Heuvelink, Annet; Ende, Arie; Smith, Hilde; Schultsz, Constance
Host-pathogen interaction at the intestinal mucosa correlates with zoonotic potential of streptococcus suis Journal Article
In: J. Infect. Dis., 212 (1), pp. 95–105, 2015.
@article{Ferrando2015-os,
title = {Host-pathogen interaction at the intestinal mucosa correlates
with zoonotic potential of streptococcus suis},
author = {Maria Laura Ferrando and Astrid Greeff and Willemien J M Rooijen and Norbert Stockhofe-Zurwieden and Jens Nielsen and Paul J Wichgers Schreur and Yvonne Pannekoek and Annet Heuvelink and Arie Ende and Hilde Smith and Constance Schultsz},
year = {2015},
date = {2015-07-01},
journal = {J. Infect. Dis.},
volume = {212},
number = {1},
pages = {95--105},
abstract = {BACKGROUND: Streptococcus suis has emerged as an important cause
of bacterial meningitis in adults. The ingestion of undercooked
pork is a risk factor for human S. suis serotype 2 (SS2)
infection. Here we provide experimental evidence indicating that
the gastrointestinal tract is an entry site of SS2 infection.
METHODS: We developed a noninvasive in vivo model to study oral
SS2 infection in piglets. We compared in vitro interaction of S.
suis with human and porcine intestinal epithelial cells (IEC).
RESULTS: Two out of 15 piglets showed clinical symptoms
compatible with S. suis infection 24-48 hours after ingestion of
SS2. SS2 was detected in mesenteric lymph nodes of 40% of
challenged piglets. SS2 strains isolated from patients showed
significantly higher adhesion to human IEC compared to invasive
strains isolated from pigs. In contrast, invasive SS9 strains
showed significantly higher adhesion to porcine IEC.
Translocation across human IEC, which occurred predominately via
a paracellular route, was significantly associated with clonal
complex 1, the predominant zoonotic genotype. Adhesion and
translocation were dependent on capsular polysaccharide
production. CONCLUSIONS: SS2 should be considered a food-borne
pathogen. S. suis interaction with human and pig IEC correlates
with S. suis serotype and genotype, which can explain the
zoonotic potential of SS2.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Streptococcus suis has emerged as an important cause
of bacterial meningitis in adults. The ingestion of undercooked
pork is a risk factor for human S. suis serotype 2 (SS2)
infection. Here we provide experimental evidence indicating that
the gastrointestinal tract is an entry site of SS2 infection.
METHODS: We developed a noninvasive in vivo model to study oral
SS2 infection in piglets. We compared in vitro interaction of S.
suis with human and porcine intestinal epithelial cells (IEC).
RESULTS: Two out of 15 piglets showed clinical symptoms
compatible with S. suis infection 24-48 hours after ingestion of
SS2. SS2 was detected in mesenteric lymph nodes of 40% of
challenged piglets. SS2 strains isolated from patients showed
significantly higher adhesion to human IEC compared to invasive
strains isolated from pigs. In contrast, invasive SS9 strains
showed significantly higher adhesion to porcine IEC.
Translocation across human IEC, which occurred predominately via
a paracellular route, was significantly associated with clonal
complex 1, the predominant zoonotic genotype. Adhesion and
translocation were dependent on capsular polysaccharide
production. CONCLUSIONS: SS2 should be considered a food-borne
pathogen. S. suis interaction with human and pig IEC correlates
with S. suis serotype and genotype, which can explain the
zoonotic potential of SS2.
of bacterial meningitis in adults. The ingestion of undercooked
pork is a risk factor for human S. suis serotype 2 (SS2)
infection. Here we provide experimental evidence indicating that
the gastrointestinal tract is an entry site of SS2 infection.
METHODS: We developed a noninvasive in vivo model to study oral
SS2 infection in piglets. We compared in vitro interaction of S.
suis with human and porcine intestinal epithelial cells (IEC).
RESULTS: Two out of 15 piglets showed clinical symptoms
compatible with S. suis infection 24-48 hours after ingestion of
SS2. SS2 was detected in mesenteric lymph nodes of 40% of
challenged piglets. SS2 strains isolated from patients showed
significantly higher adhesion to human IEC compared to invasive
strains isolated from pigs. In contrast, invasive SS9 strains
showed significantly higher adhesion to porcine IEC.
Translocation across human IEC, which occurred predominately via
a paracellular route, was significantly associated with clonal
complex 1, the predominant zoonotic genotype. Adhesion and
translocation were dependent on capsular polysaccharide
production. CONCLUSIONS: SS2 should be considered a food-borne
pathogen. S. suis interaction with human and pig IEC correlates
with S. suis serotype and genotype, which can explain the
zoonotic potential of SS2.
- Monserrato
marialaura.ferrando@cnr.it
070 6754595
ORCID_ID: 0000-0002-1398-8244
